February 19, 2019 Laurence Cooper Chief Executive Officer ZIOPHARM Oncology, Inc. One First Avenue, Parris Building 34, Navy Yard Plaza Boston, Massachusetts 02129 Re: ZIOPHARM Oncology, Inc. Registration Statement on Form S-3 Filed February 7, 2019 File No. 333-229555 Dear Mr. Cooper: This is to advise you that we have not reviewed and will not review your registration statement. Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you that the company and its management are responsible for the accuracy and adequacy of their disclosures, notwithstanding any review, comments, action or absence of action by the staff. Please contact Sonia Bednarowski at 202-551-3666 with any questions. Sincerely, Division of Corporation Finance Office of Healthcare & Insurance