Mechanistically, the hyperactivation of BNIP3-mediated mitophagy in lenvatinib-resistant HCC cells promotes glycolytic flux via shifting energy production from mitochondrial oxidative phosphorylation to glycolysis by regulating AMPK-ENO2 signaling, which perpetually maintains lenvatinib-resistant cells’ competitive dominance against sensitive HCC cells. This evidence concerns the gene PRKAA2 and hepatocellular carcinoma.