Cutaneous cancers are among the most common forms of cancer. Melanoma is an aggressive malignancy which is poor in prognosis. Despite of many years of researches, the treatment of melanoma is still a problem. Historically, plants have been main resources in traditional medicine and natural products are considered as important sources of antitumor drugs. Meanwhile, garlic for a long time has been used in man's food as a medicinal plant. In this study, the garlic extract was prepared and fractionated by ultra-filtration method with Amicon system. Garlic extract and its fractions including residue (R) 100, R50, R30, R10, R5, and filtrate (F) 5 were investigated for their cytotoxic activities on Sk-mel3 cell line of melanoma. The results show that garlic extract induced a significant cytotoxic activity on Sk-mel3 cell line. Among fractions R100 and R10 have more potential in cytotoxic activities against Sk-mel3 melanoma cells. In conclusion, garlic appears to be a good candidate as an antitumor agent against melanoma. To clarify the effective molecules and their mechanisms more studies should be applied on animal models and humans.