In order to discover structurally new and bioactive compounds from marine life, we studied the secondary metabolites of the marine-derived fungi associated with a marine sponge (XS-3) from the Xisha islands. As a result, 4- O -methylcandidusin A ( 1), a new p-terphenyl alcohol, along with nine known analogs ( 2–10), were isolated and identified from the marine sponge-derived fungus Aspergillus candidus OUCMDZ-1051. The structures of these compounds were determined by analyzing spectroscopic data, especially 1D and 2D NMR. The new compound 1 selectively inhibited the growth of the MDA-MB-468, BT474 and A431 human cancer cell lines with the IC 50 values of 1.84, 6.05 and 0.98 µmol/L, respectively. Compound 1 also displayed a selective antimicrobial activity against Escherichia coli with an MIC value of 27.3 µmol/L. The results indicated 4- O-methylcandidusin A ( 1) as a potential lead in the new drug discovery for triple negative breast cancer, invasive ductal breast cancer and epidermoid cancer. The antimicrobial metabolites also evidenced a clue for chemical defense of sponges by their associated microorganisms.