Results of the present study demonstrate that α-mangostin induces apoptotic cell death through activation of ASK1/MKK3/6/p38 signaling pathway, and inhibition of this pathway by specific inhibitors or siRNAs significantly attenuates α-mangostin-induced apoptosis in HeLa and SiHa cervical cancer cells. The gene discussed is MAP3K5; the disease is cervical carcinoma.