The three rate-limiting enzymes in the glycolytic pathway, including hexokinase 2 (HK2), phosphofructokinase 1 (PFK1), and pyruvate kinases type M2 (PKM2) play an important role in the regulation of aerobic glycolysis in HCC and can be regulated by many mechanisms, such as the AMPK, PI3K/Akt pathway, HIF-1α, c-Myc and noncoding RNAs. The gene discussed is HK2; the disease is hepatocellular carcinoma.