Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease. Its global incidence is increasing and makes NASH an epidemic and a public health threat. Non-alcoholic fatty liver disease is associated with major morbidity and mortality, with a heavy burden on quality of life and liver transplant requirements. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma. The progression of NASH was initially defined according to a two-hit model involving an initial development of steatosis, followed by a process of lipid peroxidation and inflammation. In contrast, current evidence proposes a “multi-hit” or “multi-parallel hit” model that includes multiple pathways promoting progressive fibrosis and oncogenesis. This model includes multiple cellular, genetic, immunological, metabolic, and endocrine pathways leading to hepatocellular carcinoma development, underscoring the complexity of this disease.