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  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>As
  filed with the Securities and Exchange Commission on May&nbsp;23, 2008</B>
  </DIV>
  
  
  <DIV align="right" style="font-size: 10pt; margin-top: 0pt"><B>Registration No.&nbsp;333-</B>
  </DIV>
  
  
  <DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt; margin-top:3pt">&nbsp;</DIV>
  <DIV style="width: 100%; border-bottom: 1pt solid black; font-size: 1pt">&nbsp;</DIV>
  
  
  
  
  
  
  <DIV align="center" style="font-size: 14pt; margin-top: 12pt"><B>UNITED STATES<BR>
  SECURITIES AND EXCHANGE COMMISSION</B>
  </DIV>
  
  <DIV align="center" style="font-size: 12pt"><B>Washington, D.C. 20549</B>
  </DIV>
  
  <DIV align="center" style="font-size: 18pt; margin-top: 12pt"><B>FORM S-8</B>
  </DIV>
  
  
  <DIV align="center" style="font-size: 12pt; margin-top: 12pt"><B>REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933</B>
  </DIV>
  
  <DIV align="center" style="font-size: 24pt; margin-top: 12pt"><B>RXi PHARMACEUTICALS CORPORATION</B>
  </DIV>
  
  <DIV align="center" style="font-size: 10pt">(Exact name of registrant as specified in its charter)</DIV>
  
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="47%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="47%">&nbsp;</TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD align="center" valign="top"><B>Delaware</B><BR>
  (State or other jurisdiction <BR>
  of incorporation or organization)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top"><B>20-8099512</B><BR>
  (I.R.S Employer Identification No.)</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="47%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="47%">&nbsp;</TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD align="center" valign="top"><B>60 Prescott Street, Worcester, Massachusetts</B><BR>
  (Address of Principal Executive Offices)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top"><B>01605</B><BR>
  (Zip Code)</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>RXi Pharmaceuticals Corporation 2007 Incentive Plan</B><BR>
  (Full title of the plan)</DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>Tod Woolf, Ph.D.<BR>
  Chief Executive Officer<BR>
  RXi Pharmaceuticals Corporation<BR>
  60 Prescott Street<BR>
  Worcester, Massachusetts 01605<BR>
  (508)&nbsp;767-3861</B></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt"><B>With copies to:<BR>
  Marc A. Rubenstein, Esq.<BR>
  Ropes &#038; Gray LLP<BR>
  One International Place<BR>
  Boston, Massachusetts 02110<BR>
  (617)&nbsp;951-7000</B></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 12pt">(Name, address, and telephone number, including area code, of agent for service)</DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Indicate by check mark whether the registrant is a large accelerated filer, an accelerated
  filer, a non-accelerated filer, or a smaller reporting company. See the definitions of &#147;large
  accelerated filer,&#148; &#147;accelerated filer&#148; and &#147;smaller reporting company&#148; in Rule&nbsp;12b-2 of the
  Exchange Act. (Check one):
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="22%"></TD>
      <TD width="3%"></TD>
      <TD width="22%"></TD>
      <TD width="3%"></TD>
      <TD width="22%"></TD>
      <TD width="3%"></TD>
      <TD width="22%"></TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD align="left" valign="top" nowrap>Large accelerated filer
  <FONT face="Wingdings">&#111;</FONT></TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top" nowrap>Accelerated filer
  <FONT face="Wingdings">&#111;</FONT></TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top" nowrap>Non-accelerated filer
  <FONT face="Wingdings">&#111;</FONT></TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top" nowrap>Smaller reporting company
  <FONT face="Wingdings">&#254;</FONT></TD>
  </TR>
  <TR valign="bottom">
      <TD align="center" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top" nowrap>(Do not check if a smaller reporting company)</TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top">&nbsp;</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>CALCULATION OF REGISTRATION FEE</B>
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="1%">&nbsp;</TD>
      <TD width="54%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="2%">&nbsp;</TD><!-- VRule -->
      <TD width="2%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
  
      <TD width="1%">&nbsp;</TD>
  </TR><TR style="font-size: 1px" valign="bottom">
      <TD nowrap align="left" colspan="23" style="border-bottom: 3px double #000000">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">Proposed maximum</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD nowrap align="center">Title of each class of</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">Amount to be</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">offering price</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">Proposed maximum</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">Amount of</TD>
      <TD>&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD nowrap align="center" style="border-bottom: 0px solid #000000">securities to be registered</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">registered (1)</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">per share (2)</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2" style="border-bottom: 0px solid #000000">aggregate offering price</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 1px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" colspan="2">registration fee</TD>
      <TD>&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD width="1%" style="border-top: 1px solid #000000">&nbsp;</TD>
                      <TD style="border-top: 1px solid #000000"><DIV style="margin-left:15px; text-indent:-15px">Common Stock,
  $.0001 par value
  per share</DIV></TD>
      <TD style="border-right: 1px solid #000000; border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD align="right" style="border-top: 1px solid #000000">2,750,000</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-right: 1px solid #000000; border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-top: 1x solid #000000">&nbsp;</TD>
      <TD align="left" style="border-top: 1px solid #000000">$</TD>
      <TD nowrap align="right" style="border-top: 1px solid #000000">5.00 - $7.50</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-right: 1px solid #000000; border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD align="left" style="border-top: 1px solid #000000">$</TD>
      <TD align="right" style="border-top: 1px solid #000000">15,333,372</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-right: 1px solid #000000; border-top: 1px solid #000000">&nbsp;</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD align="left" style="border-top: 1px solid #000000">$</TD>
      <TD align="right" style="border-top: 1px solid #000000">603</TD>
      <TD style="border-top: 1px solid #000000">&nbsp;</TD>
      <TD width="1%" style="border-top: 1px solid #000000">&nbsp;</TD>
  </TR>
  <TR style="font-size: 1px" valign="bottom">
      <TD nowrap align="left" colspan="23" style="border-top: 3px double #000000">&nbsp;</TD>
  </TR>
  
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  <DIV align="left">
  <DIV style="font-size: 3pt; margin-top: 6pt; width: 18%; border-top: 0px solid #000000">&nbsp;</DIV>
  </DIV>
  
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  <TR>
      <TD width="3%"></TD>
      <TD width="1%"></TD>
      <TD width="96"></TD>
  </TR>
  
  <TR valign="top">
      <TD nowrap align="left">(1)</TD>
      <TD>&nbsp;</TD>
      <TD>Pursuant to Rule 416(a) under the Securities Act of 1933, this registration statement also
  covers such additional shares as may be required pursuant to RXi Pharmaceuticals Corporation&#146;s 2007
  Incentive Plan in the event of a stock dividend, stock split, recapitalization or other similar
  change in the common stock.</TD>
  </TR>
  
  <TR style="font-size: 3pt"><TD>&nbsp;</TD></TR>
  
  <TR valign="top">
      <TD nowrap align="left">(2)</TD>
      <TD>&nbsp;</TD>
      <TD>The offering price for shares subject to options outstanding on the date hereof under the 2007
  Incentive Plan is the actual exercise price of such options. Of the 2,750,000 shares to be
  registered hereunder, 1,438,184 and 446,424 are subject to options at an exercise price of $5.00
  and $7.50 per share, respectively. The offering price of $5.54 per share for the remaining 865,392
  shares not subject to options on the date hereof has been estimated solely for the purpose of
  determining the registration fee pursuant to Rule 457(c) and 457(h)(1) on the basis of the average
  high and low prices of the Common Stock, as reported on the Nasdaq Capital Market on May&nbsp;19, 2008.</TD>
  </TR>
  
  </TABLE>
  
  
  
  <DIV style="width: 100%; border-bottom: 1pt solid black; margin-top: 10pt; font-size: 1pt">&nbsp;</DIV>
  <DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt">&nbsp;</DIV>
  
  
  
  
  
  
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  <!-- TOC -->
  <A name="toc"><DIV align="CENTER" style="page-break-before:always"><U><B>TABLE OF CONTENTS</B></U></DIV></A>
  
  <P><CENTER>
  <TABLE border="0" width="90%" cellpadding="0" cellspacing="0">
  <TR>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="76%"></TD>
  </TR>
  <TR><TD colspan="9"><A HREF="#000">PART I</A></TD></TR>
  <TR><TD colspan="9"><A HREF="#001">PART II</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#002">ITEM 3. Incorporation of Documents by Reference</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#003">ITEM 4. Description of Securities</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#004">ITEM 5. Interest of Named Experts and Counsel</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#005">ITEM 6. Indemnification of Directors and Officers</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#006">ITEM 7. Exemption from Registration Claimed</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#007">ITEM 8. Exhibits</A></TD></TR>
  <TR><TD></TD><TD colspan="8"><A HREF="#008">ITEM 9. Undertakings</A></TD></TR>
  <TR><TD colspan="9"><A HREF="#009">SIGNATURES</A></TD></TR>
  <TR><TD colspan="9"><A HREF="#010">EXHIBIT INDEX</A></TD></TR>
  <TR><TD colspan="9"><A HREF="b70204rpexv5w1.htm">EX-5.1 Opinion of Ropes & Gray LLP.</A></TD></TR>
  <TR><TD colspan="9"><A HREF="b70204rpexv23w1.htm">EX-23.1 Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm</A></TD></TR>
  </TABLE>
  </CENTER>
  <!-- /TOC -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  
  
  
  <!-- link1 "PART I" -->
  <DIV align="left"><A NAME="000"></A></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>PART I</B>
  </DIV>
  
  
  <DIV align="Center" style="font-size: 10pt; margin-top: 6pt"><B>INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS</B>
  
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The information required by Item&nbsp;1 has been sent or given to employees as specified by Rule
  428(b)(1). Such documents are not being filed with the Securities and Exchange Commission (the
  &#147;Commission&#148;) either as part of this Registration Statement or as prospectuses or prospectus
  supplements pursuant to Rule&nbsp;424. Such documents and the documents incorporated by reference in
  this Registration Statement pursuant to Item&nbsp;3 of Part&nbsp;II of this Form, taken together, constitute
  a prospectus that meets the requirements of Section 10(a) of the Securities Act.
  </DIV>
  <!-- link1 "PART II" -->
  <DIV align="left"><A NAME="001"></A></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>PART II</B>
  </DIV>
  
  
  <DIV align="Center" style="font-size: 10pt; margin-top: 6pt"><B>INFORMATION REQUIRED IN THE REGISTRATION STATEMENT</B>
  
  </DIV>
  <!-- link2 "ITEM 3. Incorporation of Documents by Reference" -->
  <DIV align="left"><A NAME="002"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 3. Incorporation of Documents by Reference.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;RXi Pharmaceuticals Corporation (the &#147;Registrant&#148;) incorporates by reference the following
  documents previously filed with the Securities and Exchange Commission (the &#147;Commission&#148;):
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(a)&nbsp;The Registrant&#146;s Annual Report on Form 10-K for the fiscal year ended December&nbsp;31, 2007
  filed with the Commission on April&nbsp;15, 2008;
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(b)&nbsp;The Registrant&#146;s Quarterly Report on Form 10-Q for the quarterly period ended March&nbsp;31,
  2008 filed with the Commission on May&nbsp;15, 2008; and
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(c)&nbsp;The description of the Common Stock, $0.0001 par value per share, contained in the
  Registrant&#146;s Registration Statement on Form 8-A/A, filed with the Commission on February&nbsp;12, 2008
  pursuant to Section&nbsp;12 of the Securities Exchange Act of 1934, as amended (the &#147;Exchange Act&#148;).
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;All documents subsequently filed by the Registrant pursuant to Sections&nbsp;13(a), 13(c), 14 and
  15(d) of the Exchange Act, prior to the filing of a post-effective amendment to this Registration
  Statement that indicates that all securities offered have been sold or which deregisters all
  securities then remaining unsold, shall be deemed to be incorporated herein by reference from the
  date of filing of such documents.
  </DIV>
  
  <!-- link2 "ITEM 4. Description of Securities" -->
  <DIV align="left"><A NAME="003"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 4. Description of Securities.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Not applicable.
  </DIV>
  
  <!-- link2 "ITEM 5. Interest of Named Experts and Counsel" -->
  <DIV align="left"><A NAME="004"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 5. Interest of Named Experts and Counsel.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Not applicable.
  </DIV>
  
  <!-- link2 "ITEM 6. Indemnification of Directors and Officers" -->
  <DIV align="left"><A NAME="005"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 6. Indemnification of Directors and Officers.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Section&nbsp;145 of the Delaware General Corporation Law provides that a corporation may indemnify
  any person who was or is a party or is threatened to be made a party to any threatened, pending or
  completed action, suit or proceeding, whether civil, criminal, administrative or investigative,
  other than an action by or in the right of the corporation, by reason of the fact that the person
  is or was a director, officer, employee or agent of the corporation or is or was serving at the
  corporation&#146;s request as a director, officer, employee or agent of another corporation,
  partnership, joint venture, trust or other enterprise, against expenses, including attorneys&#146; fees,
  judgments, fines and amounts paid in settlement actually and reasonably incurred by the person in
  connection with the action, suit or proceeding if the person acted in good faith and in a manner
  the person reasonably believed to be in or not opposed to the best interests of the corporation,
  and, with respect to any criminal action or proceeding, had no reasonable
  </DIV>
  
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">cause to believe the person&#146;s conduct was unlawful. The power to indemnify applies to actions
  brought by or in the right of the corporation as well, but only to the extent of expenses,
  including attorneys&#146; fees but excluding judgments, fines and amounts paid in settlement, actually
  and reasonably incurred by the person in connection with the defense or settlement of the action or
  suit if the person acted in good faith and in a manner the person reasonably believed to be in or
  not opposed to the best interests of the corporation and except that no indemnification shall be
  made in respect of any claim, issue or matter as to which such person shall have been adjudged to
  be liable to the corporation unless and only to the extent that a court of competent jurisdiction
  shall determine that such indemnity is proper.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">Section&nbsp;145(g) of the Delaware General Corporation Law provides that a corporation shall have the
  power to purchase and maintain insurance on behalf of its officers, directors, employees and
  agents, against any liability asserted against and incurred by such persons in any such capacity.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">Section&nbsp;102(b)(7) of the General Corporation Law of the State of Delaware provides that a
  corporation may eliminate or limit the personal liability of a director to the corporation or its
  stockholders for monetary damages for breach of fiduciary duty as a director, provided that such
  provision shall not eliminate or limit the liability of a director (i)&nbsp;for any breach of the
  director&#146;s duty of loyalty to the corporation or its stockholders, (ii)&nbsp;for acts or omissions not
  in good faith or which involve intentional misconduct or a knowing violation of law, (iii)&nbsp;under
  Section&nbsp;174 of the General Corporation Law of the State of Delaware, or (iv)&nbsp;for any transaction
  from which the director derived an improper personal benefit. No such provision shall eliminate or
  limit the liability of a director for any act or omission occurring prior to the date when such
  provision becomes effective.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">Our Amended and Restated Certificate of Incorporation provides that our directors shall not be
  liable to the Registrant or its stockholders for monetary damages for breach of fiduciary duty as a
  director, except to the extent that the exculpation from liabilities is not permitted under the
  Delaware General Corporation Law as in effect at the time such liability is determined. In
  addition, our Amended and Restated Certificate of incorporation provides that we shall indemnify
  our directors to the fullest extent permitted by the laws of the State of Delaware. We have entered
  into indemnification agreements with each of our non-employee directors that provide for
  indemnification and expense advancement to the fullest extent permitted by the laws of the State of
  Delaware.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">Our Amended and Restated Certificate of Incorporation provides that we may purchase and maintain
  insurance policies on behalf of our directors and officers against specified liabilities for
  actions taken in their capacities as such, including liabilities under the Securities Act. We have
  obtained directors and officers&#146; liability insurance to cover liabilities our directors and
  officers may incur in connection with their services to the Registrant.
  </DIV>
  
  <!-- link2 "ITEM 7. Exemption from Registration Claimed" -->
  <DIV align="left"><A NAME="006"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 7. Exemption from Registration Claimed.</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Not applicable.
  </DIV>
  
  <!-- link2 "ITEM 8. Exhibits" -->
  <DIV align="left"><A NAME="007"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 8. Exhibits.</B>
  </DIV>
  
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="2%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">4.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>2007 Incentive Plan (previously filed as Exhibit&nbsp;10.19 to the Registration
  Statement on Form S-1, as amended, No.&nbsp;333-147009, and incorporated herein
  by reference).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="2%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">4.2</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit&nbsp;3.1 to the Registration Statement on Form S-1, as amended, No.
  333-147009, and incorporated herein by reference).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="2%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">4.3</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Amended and Restated Bylaws, as amended (previously filed as Exhibit&nbsp;3.2 to
  the Registration Statement on Form S-1, as amended, No.&nbsp;333-147009, and
  incorporated herein by reference).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="2%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">5.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Opinion of Ropes &#038; Gray LLP.</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="2%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">23.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  
  <DIV style="margin-top: 6pt"><TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="2%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">23.2</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Consent of Ropes &#038; Gray, LLP (see Exhibit&nbsp;5.1).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="2%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">24.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Power of Attorney (included on the signature page hereto).</TD>
  </TR>
  
  </TABLE>
  </DIV>
  <!-- link2 "ITEM 9. Undertakings" -->
  <DIV align="left"><A NAME="008"></A></DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>ITEM 9. Undertakings.</B>
  </DIV>
  
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="3%" nowrap align="left">(a)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>The undersigned Registrant hereby undertakes:</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="4%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(1)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To file, during any period in which offers or sales are being made, a post-effective
  amendment to this Registration Statement:</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="8%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(i)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To include any prospectus required by Section&nbsp;10(a)(3) of the
  Securities Act of 1933, as amended (the &#147;Securities Act&#148;);</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="8%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(ii)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To reflect in the prospectus any facts or events arising after
  the effective date of the Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represent a fundamental change in the information set forth in the Registration
  Statement. Notwithstanding the foregoing, any increase or decrease in volume
  of securities offered (if the total dollar value of securities offered would
  not exceed that which was registered) and any deviation from the low or high
  end of the estimated maximum offering range may be reflected in the form of a
  prospectus filed with the Commission pursuant to Rule 424(b) if, in the
  aggregate, the changes in volume and price represent no more than 20&nbsp;percent
  change in the maximum aggregate offering price set forth in the &#147;Calculation of
  Registration Fee&#148; table in the effective registration statement;</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="8%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(iii)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To include any material information with respect to the plan
  of distribution not previously disclosed in the Registration Statement or any
  material change to such information in the Registration Statement;</TD>
  </TR>
  
  </TABLE>
  </DIV>
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt"><I>provided, however</I>, that paragraphs (a)(1)(i) and (a)(1)(ii) above shall not apply if the
  information required to be included in a post-effective amendment by those paragraphs is contained
  in periodic reports filed with or furnished to the Commission by the Registrant pursuant to Section
  13 or 15(d) of the Exchange Act that are incorporated by reference in the Registration Statement.
  </DIV>
  
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="4%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(2)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>That, for the purpose of determining any liability under the Securities Act,
  each such post-effective amendment shall be deemed to be a new registration statement
  relating to the securities offered therein, and the offering of such securities at that
  time shall be deemed to be the initial bona fide offering thereof.</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="4%" style="background: transparent">&nbsp;</TD>
      <TD width="3%" nowrap align="left">(3)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>To remove from registration by means of a post-effective amendment any of the
  securities being registered which remain unsold at the termination of the offering.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="3%" nowrap align="left">(b)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>The undersigned Registrant hereby undertakes that, for purposes of determining any liability
  under the Securities Act, each filing of the Registrant&#146;s annual report pursuant to Section
  13(a) or 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit
  plan&#146;s annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by
  reference in the Registration Statement shall be deemed to be a new Registration Statement
  relating to the securities offered therein, and the offering of such securities at that time
  shall be deemed to be the initial bona fide offering thereof.</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="3%" nowrap align="left">(c)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Insofar as indemnification for liabilities arising under the Securities Act may be permitted
  to directors, officers and controlling persons of the Registrant pursuant to the foregoing
  provisions, or otherwise, the Registrant has been advised that in the opinion of the
  Commission such indemnification is against public policy as expressed in the Securities Act
  and is, therefore, unenforceable. In the event that a claim for
  indemnification against such liabilities (other than the payment by the Registrant of expenses incurred or</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">paid by a director, officer or controlling person of the Registrant in the successful
  defense of any action, suit or proceeding) is asserted by such director, officer or
  controlling person in connection with the securities being registered, the Registrant will,
  unless in the opinion of its counsel the matter has been settled by controlling precedent,
  submit to a court of appropriate jurisdiction the question whether such indemnification by
  it is against public policy as expressed in the Securities Act and will be governed by the
  final adjudication of such issue.
  </DIV>
  
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  <!-- link1 "SIGNATURES" -->
  <DIV align="left"><A NAME="009"></A></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>SIGNATURES</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant
  certifies that it has reasonable grounds to believe that it meets all of the requirements for
  filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by
  the undersigned, thereunto duly authorized, in the City of Worcester, Commonwealth of Massachusetts
  on May&nbsp;23, 2008.
  </DIV>
  
  <TABLE width="100%" border="0" cellspacing="0" cellpadding="0" style="font-size: 10pt">
  <TR>
      <TD width="48%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="35%">&nbsp;</TD>
      <TD width="15%">&nbsp;</TD>
  </TR>
  <TR>
      <TD valign="top" align="left">&nbsp;</TD>
      <TD colspan="3" align="left">RXi PHARMACEUTICALS CORPORATION<BR>
  &nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD valign="top">By:&nbsp;&nbsp;</TD>
      <TD colspan="2" style="border-bottom: 1px solid #000000" align="left">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; /s/  Tod Woolf
  &nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD colspan="2" align="left">Tod Woolf, Ph.D.&nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD colspan="2" align="left">President and Chief Executive Officer&nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR>
  <TR>
      <TD colspan="5">&nbsp;</TD>
  </TR>
  </TABLE>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>POWER OF ATTORNEY</B>
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and
  appoints STEPHEN J. DIPALMA and TOD WOOLF, PH.D., and each of them, either of whom may act without
  the joinder of the other, as his true and lawful attorneys-in-fact and agents, with full power of
  substitution and resubstitution, for him and in his name, place, and stead, in any and all
  capacities, to sign any and all amendments (including post-effective amendments, exhibits thereto
  and other documents in connection therewith) to this Registration Statement, and to file the same,
  with all exhibits thereto, and other documents in connection therewith (including any registration
  statement relating to this Registration Statement and filed pursuant to Rule 462(b) of the
  Securities Act of 1933, as amended), with the Securities and Exchange Commission, granting unto
  said attorneys-in-fact and agents, and each of them, full power and authority to do and perform
  each and every act and thing requisite and necessary to be done in connection therewith, as fully
  to all intents and purposes as he might or could do in person, hereby ratifying and confirming all
  that said attorneys-in-fact and agents, or either of them, or their or his substitute or
  substitutes, may lawfully do or cause to be done by virtue hereof.
  </DIV>
  
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration
  Statement has been signed below by the following persons in the capacities and on the dates
  indicated.
  </DIV>
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="40%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="30%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="20%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">
      <TD nowrap align="center">SIGNATURES</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="left">TITLE</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="left">DATE</TD>
  </TR>
  
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Tod Woolf
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Tod Woolf, Ph.D.
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">President and Chief Executive Officer
  (Principal Executive Officer)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">May&nbsp;23, 2008</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Stephen J. DiPalma
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Stephen J. DiPalma
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="left" valign="top">Chief Financial Officer<br>
  (Principal Financial and Accounting
  Officer)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">May&nbsp;23, 2008</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Sanford J. Hillsberg
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Sanford J. Hillsberg
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">May&nbsp;23, 2008&nbsp;</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Mark J. Ahn
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Mark J. Ahn
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">May&nbsp;23, 2008</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Stephen S. Galliker
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Stephen S. Galliker
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">May&nbsp;23, 2008</TD>
  </TR>
  <TR valign="bottom"><!-- Blank Space -->
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">&nbsp;</DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom">
      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">/s/ Steven A. Kriegsman
  <DIV style="font-size: 1pt; border-top: 1px solid #000000">&nbsp;</DIV>
  Steven A. Kriegsman
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Director&nbsp;
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">May&nbsp;23, 2008</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  <P align="center" style="font-size: 10pt"><!-- Folio -->&nbsp;<!-- /Folio -->
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  <!-- link1 "EXHIBIT INDEX" -->
  <DIV align="left"><A NAME="010"></A></DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD><B>EXHIBIT INDEX</B></TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">4.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>2007 Incentive Plan (previously filed as Exhibit&nbsp;10.19 to the Registration
  Statement on Form S-1, as amended, No.&nbsp;333-147009, and incorporated herein
  by reference).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">4.2</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit&nbsp;3.1 to the Registration Statement on Form S-1, as amended, No.
  333-147009, and incorporated herein by reference).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">4.3</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Amended and Restated Bylaws, as amended (previously filed as Exhibit&nbsp;3.2 to
  the Registration Statement on Form S-1, as amended, No.&nbsp;333-147009, and
  incorporated herein by reference).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">5.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Opinion of Ropes &#038; Gray LLP.</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">23.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">23.2</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Consent of Ropes &#038; Gray, LLP (see Exhibit&nbsp;5.1).</TD>
  </TR>
  
  <TR>
      <TD style="font-size: 6pt">&nbsp;</TD>
  </TR><TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">24.1</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Power of Attorney (included on the signature page hereto).</TD>
  </TR>
  
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text: sv8
  Table of Contents
  As
  filed with the Securities and Exchange Commission on May 23, 2008
  Registration No. 333-
  UNITED STATES
  SECURITIES AND EXCHANGE COMMISSION
  Washington, D.C. 20549
  FORM S-8
  REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933
  RXi PHARMACEUTICALS CORPORATION
  (Exact name of registrant as specified in its charter)
  Delaware
  (State or other jurisdiction
  of incorporation or organization)
  20-8099512
  (I.R.S Employer Identification No.)
  60 Prescott Street, Worcester, Massachusetts
  (Address of Principal Executive Offices)
  01605
  (Zip Code)
  RXi Pharmaceuticals Corporation 2007 Incentive Plan
  (Full title of the plan)
  Tod Woolf, Ph.D.
  Chief Executive Officer
  RXi Pharmaceuticals Corporation
  60 Prescott Street
  Worcester, Massachusetts 01605
  (508) 767-3861
  With copies to:
  Marc A. Rubenstein, Esq.
  Ropes & Gray LLP
  One International Place
  Boston, Massachusetts 02110
  (617) 951-7000
  (Name, address, and telephone number, including area code, of agent for service)
  Indicate by check mark whether the registrant is a large accelerated filer, an accelerated
  filer, a non-accelerated filer, or a smaller reporting company. See the definitions of "large
  accelerated filer," "accelerated filer" and "smaller reporting company" in Rule 12b-2 of the
  Exchange Act. (Check one):
  Large accelerated filer
  o
  Accelerated filer
  o
  Non-accelerated filer
  o
  Smaller reporting company
  þ
  (Do not check if a smaller reporting company)
  CALCULATION OF REGISTRATION FEE
  Proposed maximum
  Title of each class of
  Amount to be
  offering price
  Proposed maximum
  Amount of
  securities to be registered
  registered (1)
  per share (2)
  aggregate offering price
  registration fee
  Common Stock,
  $.0001 par value
  per share
  2,750,000
  $
  5.00 - $7.50
  $
  15,333,372
  $
  603
  (1)
  Pursuant to Rule 416(a) under the Securities Act of 1933, this registration statement also
  covers such additional shares as may be required pursuant to RXi Pharmaceuticals Corporation's 2007
  Incentive Plan in the event of a stock dividend, stock split, recapitalization or other similar
  change in the common stock.
  (2)
  The offering price for shares subject to options outstanding on the date hereof under the 2007
  Incentive Plan is the actual exercise price of such options. Of the 2,750,000 shares to be
  registered hereunder, 1,438,184 and 446,424 are subject to options at an exercise price of $5.00
  and $7.50 per share, respectively. The offering price of $5.54 per share for the remaining 865,392
  shares not subject to options on the date hereof has been estimated solely for the purpose of
  determining the registration fee pursuant to Rule 457(c) and 457(h)(1) on the basis of the average
  high and low prices of the Common Stock, as reported on the Nasdaq Capital Market on May 19, 2008.
  TABLE OF CONTENTS
  PART I
  PART II
  ITEM 3. Incorporation of Documents by Reference
  ITEM 4. Description of Securities
  ITEM 5. Interest of Named Experts and Counsel
  ITEM 6. Indemnification of Directors and Officers
  ITEM 7. Exemption from Registration Claimed
  ITEM 8. Exhibits
  ITEM 9. Undertakings
  SIGNATURES
  EXHIBIT INDEX
  EX-5.1 Opinion of Ropes & Gray LLP.
  EX-23.1 Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm
  Table of Contents
  PART I
  INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
  The information required by Item 1 has been sent or given to employees as specified by Rule
  428(b)(1). Such documents are not being filed with the Securities and Exchange Commission (the
  "Commission") either as part of this Registration Statement or as prospectuses or prospectus
  supplements pursuant to Rule 424. Such documents and the documents incorporated by reference in
  this Registration Statement pursuant to Item 3 of Part II of this Form, taken together, constitute
  a prospectus that meets the requirements of Section 10(a) of the Securities Act.
  PART II
  INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
  ITEM 3. Incorporation of Documents by Reference.
  RXi Pharmaceuticals Corporation (the "Registrant") incorporates by reference the following
  documents previously filed with the Securities and Exchange Commission (the "Commission"):
  (a) The Registrant's Annual Report on Form 10-K for the fiscal year ended December 31, 2007
  filed with the Commission on April 15, 2008;
  (b) The Registrant's Quarterly Report on Form 10-Q for the quarterly period ended March 31,
  2008 filed with the Commission on May 15, 2008; and
  (c) The description of the Common Stock, $0.0001 par value per share, contained in the
  Registrant's Registration Statement on Form 8-A/A, filed with the Commission on February 12, 2008
  pursuant to Section 12 of the Securities Exchange Act of 1934, as amended (the "Exchange Act").
  All documents subsequently filed by the Registrant pursuant to Sections 13(a), 13(c), 14 and
  15(d) of the Exchange Act, prior to the filing of a post-effective amendment to this Registration
  Statement that indicates that all securities offered have been sold or which deregisters all
  securities then remaining unsold, shall be deemed to be incorporated herein by reference from the
  date of filing of such documents.
  ITEM 4. Description of Securities.
  Not applicable.
  ITEM 5. Interest of Named Experts and Counsel.
  Not applicable.
  ITEM 6. Indemnification of Directors and Officers.
  Section 145 of the Delaware General Corporation Law provides that a corporation may indemnify
  any person who was or is a party or is threatened to be made a party to any threatened, pending or
  completed action, suit or proceeding, whether civil, criminal, administrative or investigative,
  other than an action by or in the right of the corporation, by reason of the fact that the person
  is or was a director, officer, employee or agent of the corporation or is or was serving at the
  corporation's request as a director, officer, employee or agent of another corporation,
  partnership, joint venture, trust or other enterprise, against expenses, including attorneys' fees,
  judgments, fines and amounts paid in settlement actually and reasonably incurred by the person in
  connection with the action, suit or proceeding if the person acted in good faith and in a manner
  the person reasonably believed to be in or not opposed to the best interests of the corporation,
  and, with respect to any criminal action or proceeding, had no reasonable
  Table of Contents
  cause to believe the person's conduct was unlawful. The power to indemnify applies to actions
  brought by or in the right of the corporation as well, but only to the extent of expenses,
  including attorneys' fees but excluding judgments, fines and amounts paid in settlement, actually
  and reasonably incurred by the person in connection with the defense or settlement of the action or
  suit if the person acted in good faith and in a manner the person reasonably believed to be in or
  not opposed to the best interests of the corporation and except that no indemnification shall be
  made in respect of any claim, issue or matter as to which such person shall have been adjudged to
  be liable to the corporation unless and only to the extent that a court of competent jurisdiction
  shall determine that such indemnity is proper.
  Section 145(g) of the Delaware General Corporation Law provides that a corporation shall have the
  power to purchase and maintain insurance on behalf of its officers, directors, employees and
  agents, against any liability asserted against and incurred by such persons in any such capacity.
  Section 102(b)(7) of the General Corporation Law of the State of Delaware provides that a
  corporation may eliminate or limit the personal liability of a director to the corporation or its
  stockholders for monetary damages for breach of fiduciary duty as a director, provided that such
  provision shall not eliminate or limit the liability of a director (i) for any breach of the
  director's duty of loyalty to the corporation or its stockholders, (ii) for acts or omissions not
  in good faith or which involve intentional misconduct or a knowing violation of law, (iii) under
  Section 174 of the General Corporation Law of the State of Delaware, or (iv) for any transaction
  from which the director derived an improper personal benefit. No such provision shall eliminate or
  limit the liability of a director for any act or omission occurring prior to the date when such
  provision becomes effective.
  Our Amended and Restated Certificate of Incorporation provides that our directors shall not be
  liable to the Registrant or its stockholders for monetary damages for breach of fiduciary duty as a
  director, except to the extent that the exculpation from liabilities is not permitted under the
  Delaware General Corporation Law as in effect at the time such liability is determined. In
  addition, our Amended and Restated Certificate of incorporation provides that we shall indemnify
  our directors to the fullest extent permitted by the laws of the State of Delaware. We have entered
  into indemnification agreements with each of our non-employee directors that provide for
  indemnification and expense advancement to the fullest extent permitted by the laws of the State of
  Delaware.
  Our Amended and Restated Certificate of Incorporation provides that we may purchase and maintain
  insurance policies on behalf of our directors and officers against specified liabilities for
  actions taken in their capacities as such, including liabilities under the Securities Act. We have
  obtained directors and officers' liability insurance to cover liabilities our directors and
  officers may incur in connection with their services to the Registrant.
  ITEM 7. Exemption from Registration Claimed.
  Not applicable.
  ITEM 8. Exhibits.
  4.1
  2007 Incentive Plan (previously filed as Exhibit 10.19 to the Registration
  Statement on Form S-1, as amended, No. 333-147009, and incorporated herein
  by reference).
  4.2
  Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit 3.1 to the Registration Statement on Form S-1, as amended, No.
  333-147009, and incorporated herein by reference).
  4.3
  Amended and Restated Bylaws, as amended (previously filed as Exhibit 3.2 to
  the Registration Statement on Form S-1, as amended, No. 333-147009, and
  incorporated herein by reference).
  5.1
  Opinion of Ropes & Gray LLP.
  23.1
  Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.
  Table of Contents
  23.2
  Consent of Ropes & Gray, LLP (see Exhibit 5.1).
  24.1
  Power of Attorney (included on the signature page hereto).
  ITEM 9. Undertakings.
  (a)
  The undersigned Registrant hereby undertakes:
  (1)
  To file, during any period in which offers or sales are being made, a post-effective
  amendment to this Registration Statement:
  (i)
  To include any prospectus required by Section 10(a)(3) of the
  Securities Act of 1933, as amended (the "Securities Act");
  (ii)
  To reflect in the prospectus any facts or events arising after
  the effective date of the Registration Statement (or the most recent
  post-effective amendment thereof) which, individually or in the aggregate,
  represent a fundamental change in the information set forth in the Registration
  Statement. Notwithstanding the foregoing, any increase or decrease in volume
  of securities offered (if the total dollar value of securities offered would
  not exceed that which was registered) and any deviation from the low or high
  end of the estimated maximum offering range may be reflected in the form of a
  prospectus filed with the Commission pursuant to Rule 424(b) if, in the
  aggregate, the changes in volume and price represent no more than 20 percent
  change in the maximum aggregate offering price set forth in the "Calculation of
  Registration Fee" table in the effective registration statement;
  (iii)
  To include any material information with respect to the plan
  of distribution not previously disclosed in the Registration Statement or any
  material change to such information in the Registration Statement;
  provided, however
  , that paragraphs (a)(1)(i) and (a)(1)(ii) above shall not apply if the
  information required to be included in a post-effective amendment by those paragraphs is contained
  in periodic reports filed with or furnished to the Commission by the Registrant pursuant to Section
  13 or 15(d) of the Exchange Act that are incorporated by reference in the Registration Statement.
  (2)
  That, for the purpose of determining any liability under the Securities Act,
  each such post-effective amendment shall be deemed to be a new registration statement
  relating to the securities offered therein, and the offering of such securities at that
  time shall be deemed to be the initial bona fide offering thereof.
  (3)
  To remove from registration by means of a post-effective amendment any of the
  securities being registered which remain unsold at the termination of the offering.
  (b)
  The undersigned Registrant hereby undertakes that, for purposes of determining any liability
  under the Securities Act, each filing of the Registrant's annual report pursuant to Section
  13(a) or 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit
  plan's annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by
  reference in the Registration Statement shall be deemed to be a new Registration Statement
  relating to the securities offered therein, and the offering of such securities at that time
  shall be deemed to be the initial bona fide offering thereof.
  (c)
  Insofar as indemnification for liabilities arising under the Securities Act may be permitted
  to directors, officers and controlling persons of the Registrant pursuant to the foregoing
  provisions, or otherwise, the Registrant has been advised that in the opinion of the
  Commission such indemnification is against public policy as expressed in the Securities Act
  and is, therefore, unenforceable. In the event that a claim for
  indemnification against such liabilities (other than the payment by the Registrant of expenses incurred or
  Table of Contents
  paid by a director, officer or controlling person of the Registrant in the successful
  defense of any action, suit or proceeding) is asserted by such director, officer or
  controlling person in connection with the securities being registered, the Registrant will,
  unless in the opinion of its counsel the matter has been settled by controlling precedent,
  submit to a court of appropriate jurisdiction the question whether such indemnification by
  it is against public policy as expressed in the Securities Act and will be governed by the
  final adjudication of such issue.
  Table of Contents
  SIGNATURES
  Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant
  certifies that it has reasonable grounds to believe that it meets all of the requirements for
  filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by
  the undersigned, thereunto duly authorized, in the City of Worcester, Commonwealth of Massachusetts
  on May 23, 2008.
  RXi PHARMACEUTICALS CORPORATION
  By:
  /s/  Tod Woolf
  Tod Woolf, Ph.D.
  President and Chief Executive Officer
  POWER OF ATTORNEY
  KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and
  appoints STEPHEN J. DIPALMA and TOD WOOLF, PH.D., and each of them, either of whom may act without
  the joinder of the other, as his true and lawful attorneys-in-fact and agents, with full power of
  substitution and resubstitution, for him and in his name, place, and stead, in any and all
  capacities, to sign any and all amendments (including post-effective amendments, exhibits thereto
  and other documents in connection therewith) to this Registration Statement, and to file the same,
  with all exhibits thereto, and other documents in connection therewith (including any registration
  statement relating to this Registration Statement and filed pursuant to Rule 462(b) of the
  Securities Act of 1933, as amended), with the Securities and Exchange Commission, granting unto
  said attorneys-in-fact and agents, and each of them, full power and authority to do and perform
  each and every act and thing requisite and necessary to be done in connection therewith, as fully
  to all intents and purposes as he might or could do in person, hereby ratifying and confirming all
  that said attorneys-in-fact and agents, or either of them, or their or his substitute or
  substitutes, may lawfully do or cause to be done by virtue hereof.
  Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration
  Statement has been signed below by the following persons in the capacities and on the dates
  indicated.
  SIGNATURES
  TITLE
  DATE
  /s/ Tod Woolf
  Tod Woolf, Ph.D.
  President and Chief Executive Officer
  (Principal Executive Officer)
  May 23, 2008
  /s/ Stephen J. DiPalma
  Stephen J. DiPalma
  Chief Financial Officer
  (Principal Financial and Accounting
  Officer)
  May 23, 2008
  /s/ Sanford J. Hillsberg
  Sanford J. Hillsberg
  Director
  May 23, 2008
  /s/ Mark J. Ahn
  Mark J. Ahn
  Director
  May 23, 2008
  /s/ Stephen S. Galliker
  Stephen S. Galliker
  Director
  May 23, 2008
  /s/ Steven A. Kriegsman
  Steven A. Kriegsman
  Director
  May 23, 2008
  Table of Contents
  EXHIBIT INDEX
  4.1
  2007 Incentive Plan (previously filed as Exhibit 10.19 to the Registration
  Statement on Form S-1, as amended, No. 333-147009, and incorporated herein
  by reference).
  4.2
  Amended and Restated Certificate of Incorporation (previously filed as
  Exhibit 3.1 to the Registration Statement on Form S-1, as amended, No.
  333-147009, and incorporated herein by reference).
  4.3
  Amended and Restated Bylaws, as amended (previously filed as Exhibit 3.2 to
  the Registration Statement on Form S-1, as amended, No. 333-147009, and
  incorporated herein by reference).
  5.1
  Opinion of Ropes & Gray LLP.
  23.1
  Consent of BDO Seidman, LLP, Independent Registered Public Accounting Firm.
  23.2
  Consent of Ropes & Gray, LLP (see Exhibit 5.1).
  24.1
  Power of Attorney (included on the signature page hereto).