Moreover, increased ENO2 expression and attenuated inhibitory effects of ENO2 knockdown on glycolysis activities under AMPK activation, unchanged BNIP3 expression and mitophagy colocalization under AMPK inhibition or activation, decreased inhibitory influence of AMPK-IN-3 on AMPK expression and glycolysis activities and population advantage under BNIP3 overexpression and previous BNIP3-ENO2 regulatory axis first reveal a vital role for BNIP3-AMPK-ENO2 crosstalk in continuously maintaining competitive advantage of lenvatinib-resistant HCC cells (CCHuh7R/CCPLC-PRF-5R). This evidence concerns the gene ENO2 and hepatocellular carcinoma.