Functional validation included <i>in vitro</i> CCK8 and Transwell assays in Huh7 cells and <i>in vivo</i> xenograft experiments combining the LDHA inhibitor (R)-GNE-140 with a PD-1 antibody.<h4>Results</h4>Post-ICI, HCC cells upregulated pyruvate metabolism genes (LDHA, LDHB, LDHD) but showed decreased glycolysis, lactate buildup, reduced acetylation, and suppressed TCA cycle with AMPK activation. Here, LDHB is linked to hepatocellular carcinoma.