<jats:title>Abstract</jats:title> <jats:p>A new cytochalasin, named cytochalasin P<jats:sub>1</jats:sub> (<jats:bold>1</jats:bold>), together with four known analogs (<jats:bold>2–5</jats:bold>) was isolated from marine-derived fungus <jats:italic>Xylaria</jats:italic> sp. SOF11 from the South China Sea. The structure of the new compound was elucidated on the basis of MS and NMR (<jats:sup>1</jats:sup>H, <jats:sup>13</jats:sup>C, HSQC, HMBC, and NOESY) data analyses. Compounds <jats:bold>1–5</jats:bold> were tested for their cytotoxicities against four tumor cell lines (SF-268, MCF-7, NCI-H460, and HepG-2). Compounds <jats:bold>1–5</jats:bold> showed significant cytotoxicity against two tumor cell lines MCF-7 and SF-268, with the IC<jats:sub>50</jats:sub> values varying between 0.33 and 4.17 μM.