The metabolic energy consumption relies primarily on mitochondrial OXPHOS in a healthy liver. Once the liver starts to subsequent damage induced by oxidative stress, and lipids accumulation, which may lead to NAFLD. In the early stages of NASH, mitochondrial adaptations are lost, which includes a low mitochondrial respiratory function. Finally, a metabolic shift from mitochondrial OXPHOS to glycolysis accompanied by a decrease in mitochondrial mass occurs during malignant transformation to PLC. Abbreviation: NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PLC, Primary liver cancer.