Restoration of cancer cells susceptibility to TRAIL-induced apoptosis is becoming a very useful strategy for cancer therapy.28 In this study, we provided evidence that rotenone increased the apoptosis sensitivity of NSCLC cells toward TRAIL by mechanisms involving ROS generation, p53 upregulation, Bcl-XL and c-FLIP downregulation, and death receptors upregulation. Here, TP53 is linked to cancer.