Silencing of HK2 leads to a reduction in glucose flux to pyruvate and lactate (glycolysis), but the tricarboxylic acid (TCA) cycle (OXPHOS) is unchanged. Depletion of HK2 synergistic with sorafenib sensitizes HCC cells to cell death and inhibits the mTORC1, together with metformin. This evidence concerns the gene HK2 and hepatocellular carcinoma.