In summary, we established the first proof of concept that targeting PGAM1 not only restrains HCC growth by promoting ferroptosis via energy stress/ROS‐dependent degradation of the AKT/LCN2 axis but also downregulates PD‐L1, thus potentiating robust CD8+ T‐cell‐mediated antitumor immunity and synergizing with anti‐PD‐1 immunotherapy (Figure 6M). This evidence concerns the gene CD274 and hepatocellular carcinoma.