Background and aims: The sea cucumbers were considered as an important component of aquatic ecosystems in more marine ecosystems. Melanoma as the most dangerous form of skin cancer, has long been influenced the human health. In the present study was examined the cytotoxic effect of sea cucumber body wall extract, species of Holothuria arenicola on melanoma cancer cells. Methods: In this in vitro experimental study, melanoma cancer cells were cultured in %10 RPMI 1640(Roswell Park Memorial Institute) medium and incubated at 37˚C with %5 CO2. After 24 h, the cells were treated by sea cucumber extract with different concentrations (15, 31, 62, 125, 250, 500 &mug/ml). The cytotoxic effect of sea cucumber body wall extract were examined by using MTT assay, Acridine Orange/ Propodium Iodide, DAPI staining, flow cytometry and caspase 3, 9 assay on melanoma cancer cells and the results were analyzed by SPSS software, one way ANOVA and Duncan test. Results: Sea cucumber body wall extract were induced cytotoxic effect through apoptosis induction on B16F10 melanoma cancer cells after 24 h treatment with IC50= 34 µg/ml. This extract were exerted more toxicity in concentration of 62 µg/ml as a result around 80% of the cells were apoptotic. Conclusion: Our findings indicated that the sea cucumber body wall extract with cytotoxic and pro apoptosis activity in B16F10cell line can be a good candidate for anti-cancer researches.