The results of the present study showed that transient p53 knockdown attenuated I3M-induced ROS production in HCT116 p53+/+ cells and that NAC treatment downregulated DR5 expression and cancer cell death, indicating that I3M-mediated p53 enhances ROS production and consequently triggers TRAIL-mediated apoptosis by inducing DR5 expression. This evidence concerns the gene TNFRSF10B and cancer.