In CRC, SELENOP enhances the WNT/β‐catenin pathway by binding to WNT3A and LRP5/6, accelerating APC loss‐driven tumorigenesis; in HCC, low SELENOP expression is associated with lipid metabolism disorders (downregulation of PPARA/APOC3), abnormal hormone receptors, impaired antioxidant capacity, and promotion of hypoxic microenvironment. Here, LRP5 is linked to hepatocellular carcinoma.