In conclusion, we focused on the p53 status and regulation of tNOX expression in HCT116 human colon cancer p53-wild-type and –null cells and show that ROS generation and p53 activation cooperatively act to inhibit POU3F2 and tNOX to promote apoptosis in p53-wild-type cells. This evidence concerns the gene ENOX2 and malignant colon neoplasm.