The aim of this study is to explore inhibitory activity of Bifidobacterium adolescent combined with cisplatin on the growth of melanoma (B16) in mice and the underlying mechanism. C57 mice were inoculated with B16 cancer cells to construct mouse model of melanoma and treated with bifidobacterium adolescent combined with cisplatin. Ratios of inhibitory activity on the growth of melanoma (B16) were calculated. Pathology changes of the tumor were observed by HE staining. B16 cell cycles were examined on a flow cytometer. Lymphocyte proliferation was measured with MTT assay and the T-cell subset was measured by double marked fluorescence. When bifidobacterium of 10 cfu/L was injected, the ratio of inhibitory activity on the growth of melanoma (B16) reached 54%, which was similar to that of cisplatin group. The ratio of inhibitory activity reached 74.45% when the mice were treated by bifidobacterium combined with cisplatin. HE staining shows that bifidobacterium inhibited B16 cell proliferation and enhanced the cisplatins killing activity on B16 cells. The results of flow cytometry demonstrated that B16 cell proliferation was arrested at G stage after treatment with bifidobacterium. The B16 cell proliferation was arrested at S stage after treatment with cisplatin. The CD4+ percentage increased and the difference was significant compared with the normal group after treatment with bifidobacterium, indicating that T-cell immune activity was enhanced. Treatment with bifidobacterium combined with cisplatin can enhance the inhibitory activity on the growth of melanoma (B16) of cisplatin. The mechanism of the inhibitory activity on B16 cell proliferation is correlated with the enhanced immune activity in mice.