Activation of TRPM8 channel through oxidative stress may induce Ca2+ and pro-apoptotic signals in prostate cancer and kidney cells. The aim of this study was to evaluate activation of TRPM8 can increase apoptosis and oxidative stress in the prostate cancer (Du145(M8)), TRPM8 knock out (Du 145(M8KO)), transfected (HEK293(TM8)) and non-transfected human kidney (HEK293) cells. Intracellular Ca2+ responses to TRPM8 activation were increased in the Du145(M8) and HEK293(TM8) cells from coming cumene hydrogen peroxide (CHPx), menthol, ADP-Ribose (ADPR), but not in the HEK293 and Du 145(M8KO) cells. The intracellular Ca2+ responses to both ADPR and CHPx were totally inhibited by the thiol cycle antioxidant glutathione, and TRPM8 blockers (N-(p-amylcinnamoyl) anthranilic acid and capsazepine). Apoptosis, Annexin V, mitochondrial membrane depolarization, intracellular ROS, caspase 3 and 9 values were increased through TRPM8 activation in the Du 145(M8) but not in the Du 145(M8KO) and non-transfected HEK293 cells by CHPx and hydrogen peroxide. In conclusion, apoptotic and oxidant effects on the cells were increased activation of TRPM8 by oxidative stress and ADPR. Activation of TRPM8 through oxidative stress and ADPR in the cells could be used as an effective strategy in the treatment of prostate cancer cells.