As we also showed concordant STAT3-AR-CCRK-mTORC1 signaling activation in patients with NASH-associated HCC, our findings unveil a central role of CCRK as a molecular hub of multiple metabolic and immunosuppressive cascades, and offer a novel therapeutic target for HCC intervention in the era of obesity epidemic. Here, CDK20 is linked to obesity due to melanocortin 4 receptor deficiency.