SOX9 has emerged as a potential therapeutic target for various types of cancer.[6] We and others initially identified that SOX9 is one of the key factors critical for maintaining the self‐renewal and pluripotency of tumor‐initiating cells or cancer stem cells (CSCs) in HCC and lung carcinoma.[12, 14, 40] Although previous studies indicate that FBW7 regulates SOX9 protein levels by promoting SOX9 ubiquitination and degradation,[10, 11] our work provides evidence to support that KEAP1 can also directly control SOX9 stability in a posttranslational manner. This evidence concerns the gene KEAP1 and hepatocellular carcinoma.