To study the metabolites of mangrove fungus Penicillium oxalicum from the south China sea and search for new anti-tumor compounds. METHODS AND RESULTS:Compounds were isolated by silica gel,ODS column chromatography,Sephadex LH-20 column chromatography and reversed-phase HPLC purification.Structural elucidation was achieved by physico-chemical constants and spectroscopic analysis.MTT assay was used to evaluate the bioactivities in vitro.Six cyclic dipeptides were isolated from the acetone extracts of mycelium of fungus and elucidated as cyclo-(Phe-Ile)(1),Cyclo(Phe-Val)(3),cyclo-(Ile-Leu)(3),cyclo-(Val-Val)(4),cyclo-(Pro-Val)(5),cyclo-(Pro-Gly)(6).Coumpouds 2,3 and 5 could evidently inhibit the growth of cancer cell lines HepG Ⅱ and LNCaP at the concentration of 50 μg·mL-1. CONCLUSIONS: All of Compounds are obtained from the marine fungus for the fist time.Compounds 2,3 and 5 show cytotoxic activity in vitro.