There is no information about the effect of polysaccharides from fungus, Phellinus gilvus (PG) on melanoma. The effect of PG on the proliferation and apoptosis of the B16F10 melanoma cell line was determined by a sulforhodamine B (SRB) and a sandwich enzyme-linked immunosorbent assay. The in vivo effect of PG on B16F10 melanoma cells allografted in athymic nude mice was investigated. PG decreased cell proliferation and increased cell apoptosis in a dose dependent manner in vitro. Also, PG significantly inhibits melanoma growth in mice. The PG anti-tumor effect in vivo was associated with a significant increase in the melanoma apoptosis rate. These findings support PG as a therapeutic agent against melanoma.