Melanoma is highly resistant to most traditional treatments; therefore, its incidence and mortality rates are rapidly increasing. The effect of a novel sansalvamide A analogue named LY-15 on the growth and induction of apoptosis in B16 cancer cells was investigated in vitro. The inhibitory effects of LY-15 on B16 cells occurred in a concentration- and time-dependent manner. The B16 cells were cultured in various concentrations of LY-15 (5, 15 and 25 ?M), and the ameliorating effect of LY-15 was evaluated using apoptotic protein markers B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3 and caspase-9. Furthermore, LY-15 effectively inhibited the B16 cell migration, increased the expressions levels of caspase-3, caspase-9 and the pro-apoptotic Bax, and reduced that of the anti-apoptotic Bcl-2. These findings suggested that LY-15 is a promising chemotherapeutic agent against melanoma by inducing apoptosis through the mitochondrial-associated death pathway. In addition, sansalvamide A analogue LY-15 may a significant therapeutic target for the treatment of malignant melanoma cancer.