Chemical investigation of the mangrove fungal endophytes, Phomopsis spp. xy21 and xy22, afforded four new cytochalasins, named phomopsichalasins D-G, along with six known analogues. The structures of these cytochalasins were elucidated on the basis of HRESIMS and extensive NMR spectroscopic data. Phomopsichalasins D (1) and E (2) represent the first two 10-phenyl[11]-cytochalasans containing a 12 carboxyl function. All of the isolates were evaluated for their cytotoxicities against eight human cancer cell lines by the MTT method. Phomopsichalasin G (4) exhibited inhibitory activities against HCT-8, HCT-8/T, A549, MDA-MB-231, and A2780 cancer cell lines with IC50 values of 7.5, 8.6, 6.4, 3.4, and 7.1mM, respectively.