Our study provides evidence that STAT3 promotes HCC cell glycolysis metabolism via HK2 and the mTOR-STAT3-HK2 pathway is involved in the glycolysis of HCC cells, suggesting the potential by blocking HCC glycolysis through targeting multiple molecules of mTOR-STAT3-HK2 pathway in HCC treatment. The gene discussed is STAT3; the disease is hepatocellular carcinoma.