OBJECTIVE: To study the effects of Coriolus versicolor polysaccharides (CVP) on in vitro proliferation and apoptosis of murine melanoma B16 cell and its mechanism. METHODS: MTT assay was used to determine the survival rate of murine melanoma B16 cell after cultured with DMSO (negative control), 0 (blank control), 0.156, 0.312 5, 0.625, 1.25, 2.5, 5.0 and 10.0 μg/ml CVP for 48, 72 h, and the IC50 was calculated. Flow cytometry was used to determine the apoptotic rate of murine melanoma B16 cell after cultured with DMSO (negative control), 0 (blank control), 0.5 μg/ml CVP for 24, 48, 72 h. Quantitation Real-time PCR (qRT-PCR) was used to determine the mRNA expression of cell apoptosis-related gene P53, Bcl-2 and Fas in murine melanoma B16 cell after cultured with DMSO (negative control), 0.5 μg/ml CVP for 48, 72 h. RESULTS: 0.156-10.0 μg/ml CVP could inhibit the growth of B16 cells, in concentration and time-dependent manner within 0.156-0.625 μg/ml; IC50 of B16 cells after cultured for 48 and 72 h were (0.32±0.01),(0.18±0.04) μg/ml. After cultured with 0.5 μg/ml CVP for 24, 48, 72 h, apoptotic rates of B16 cells were increased significantly, compared to negative control and blank control (P<0.01). After cultured with 0.5 μg/ml CVP for 48, 72 h, mRNA expression of P53, Bcl-2 and Fas were decreased significantly, compared to negative control (P<0.01). CONCLUSIONS: CVP can inhibit the proliferation and induce the apoptosis of B16 cells, the mechanism of which may be associated with the expression down-regulation of P53, Bcl-2 and Fas gene.