Taken together, this study uncovers a therapeutic vulnerability for HCC based on the role of HKDC1 in promoting tumor immune evasion through recruitment of cytosolic STAT1 to IFNGR1 on the plasma membrane, and suggests that a combination treatment strategy targeting both HKDC1 and ICB could be an effective route for developing of HCC interventions. Here, HKDC1 is linked to hepatocellular carcinoma.