WWOX P282A variant, a SNP rs3764340, has been reported to be associated with the susceptibility to many malignant tumors, including gastric cancer, lung cancer, oral cancer, osteosarcoma, thyroid carcinoma, hepatocellular carcinoma, and esophageal cancer.[50] Proline‐282‐alanine substitution may cause a change in WWOX protein structure, thereby affecting the function of the tumor suppressor.[30] Our study provides the first experimental evidence, demonstrating that the WWOXP282A mutant protein lost the ability of a tumor suppressor. This evidence concerns the gene WWOX and hepatocellular carcinoma.