Skin cancer has been reported as a contemporary malignant cancer. Here, anti-cancer effects of sea cucumber extract (SCE) from Holothuria arenicola have been examined on melanoma cells and compared with imidazole carboxamide (Dacarbazine) as a chemotherapy medication against melanoma and Hodgkin's lymphoma. MTT assay and morphological analysis were performed to evaluate cytotoxic effects of H. arenicola extract. Also, several methods were exerted to detect cell dying by SCE and imidazole carboxamide. The MTT assay showed that B16F10 cells proliferation was blocked by SCE (IC50=31μ g ml-1) and imidazole carboxamide (IC50=1600 μ g ml-1) in a dose and time dependent manner. Apoptosis induction yield treatment occurred at IC50 concentration of SCE and imidazole carboxamide using DAPI staining, Acridine orange/Propodium iodide, PI flow cytometry and annexin/PI assay. The caspase colorimetric kit indicated that SCE and imidazole carboxamide could induce apoptosis through an intrinsic pathway. Collectively, our findings suggested that the methanolic SCE has more efficient cytotoxicity efficiency compared to imidazole carboxamide. Therefore, SCE may be considered as a futuristic marine natural product regarding prevention or treatment of melanoma malignancy.