In summary, our study reported that mitophagy can profoundly boost shifting energy production from mitochondrial oxidative phosphorylation to glycolysis via BNIP3-AMPK-ENO2 signaling, thereby maintaining lenvatinib-resistant HCC cells’ growth and leading to HCC development through sacrificing sensitive cells in cell competition scenario. The gene discussed is PRKAA2; the disease is hepatocellular carcinoma.