The secondary metabolites of strain Penicillium chrysogenum, an epiphytic fungus isolated from the Xisha sponge T. swinhoei were studied, in order to find structurally specific secondary metabolites. The fungus Penicillium chrysogenum was fermented with Fungus No.2 medium, the mycelium was extracted and purified by modern chromatography method including repeated column chromatography on silica gel, ODS and semi-preparative HPLC. The structures of isolated compounds were identified with modern spectroscopic techniques combined with HRMS. The results showed that seven compounds were isolated from the mycelium of strain Penicillium chrysogenum, which was isolated from the sponge T.swinhoei. They were identified as Traumatic acid (1),N-benzoyl-L-phenylalaninol (2),cyclo-(Trp-Ser) (3),cyclo-(D-Pro-D-Leu) (4),cyclo-(Phe-Tyr)(5),(22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,9(11),22-trien-3β-ol(6),5α,8α-epidioxy-23-methyl-(22E,24S)-ergosta-6,22-dien-3β-ol(7).Compound 1 was initially isolated from nature and compounds 2, 3, 4, 5, 6 and 7 were isolated from Penicillium chrysogenum for the first time.