In this study, we found that overexpression of MDM4 in mutant p53 colon cancer cells was able to increase the expression level of GPX4, and knockdown of MDM4 was followed by a decrease in the protein expression level of GPX4, which also provided strong evidence for the conclusion that MDM4 inhibited ferroptosis in mutant p53 colon cancer. Here, MDM4 is linked to malignant colon neoplasm.