Our results revealed that XAV‐939 and ICG‐001 attenuated the elevated levels of ECAR and extracellular lactate induced by ASPP2 knockdown, suggesting that ASPP2 inhibits aerobic glycolysis of HCC by inhibiting glycolysis kinase expression via the WNT/β‐catenin signalling. The gene discussed is TP53BP2; the disease is hepatocellular carcinoma.