Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide. It is an aggressive cancer with low cure rate, frequent metastasis, and highly resistant to conventional chemotherapies. Better knowledge regarding the molecular and metabolic alterations in HCC will be instrumental to the development of novel therapeutic interventions against HCC. In the August 2015 issue of Hepatology, Nie et al. reports an important molecular pathway that contributes to the Warburg Effect in HCC. They have beautifully demonstrated that the loss of a component of a hormonal system, the mineralocorticoid receptor (MR), reprogrammed the metabolic machinery of HCC cells to aerobic glycolysis through the miR-338-3p-PKL/R axis. The implication could be that in addition to drugs that directly target the metabolic enzymes in cancer cells, more translational efforts could be focused on the development of drugs that involve the activation of the MR-aldosterone system or other hormonal systems to target the Warburg effect.