Cancer radical surgery is the primary treatment for melanoma, but almost all malignant melanoma patients get recurrence and metastasis after surgery and are eventually dead. This clinical dilemma appeals to better drugs for post-surgery therapy. Artemisinin is a safe and effective antimalarial drug used in the clinic for decades. However, no information is available regarding the effect of Artemisinins on melanoma recurrence and metastasis after tumor excision. In the present study, we established a post-surgery tumor model on balb/c nude mice, and we found that subclinical dosages of Artemisinin significantly blocked recurrence, metastasis, and extended survival time of mice after tumor excision. Similar results were obtained in the in vitro experiments with B16 and A375 cell lines. Further experiments confirmed that Artemisinin inhibits melanoma in vitro and in vivo after radical surgery by the c-KIT/PI3K/AKT signaling pathway. Our findings support the therapeutic potential of Artemisinin in malignant melanoma after surgery.