A previous drug screening showed that α-Mangostin significantly down-regulate MITF expression.17 MITF participates in the senescence, apoptosis, proliferation, cell cycle, migration and invasion of melanoma cells by regulating important signal molecules such as TBX2, CDK2, CDKN1A/B, CDKN2A, Bcl-2, C-Met and HIF-1 α.20, 32-34 In the present study, we evaluated whether α-Mangostin regulated the expression of MITF and biological events in melanoma. The gene discussed is CDKN1A; the disease is melanoma.