The evidence for a possible link between Non-alcoholic steatohepatitis (NASH) and Hepatocellular carcinoma (HCC) is clearly emerging. A significant proportion of HCC cases develop in cryptogenic cirrhosis, which is associated with obesity and diabetes, main risk factors for NASH. In longitudinal studies, HCC appears to be a rare and long-term complication of NASH, with a prevalence ranging from 0%-2.8% over 20 years. However, once cirrhosis had developed 4%-27% of cases can be complicated by HCC. Diagnostic delay as well as the older age and the concurrent presence of severe metabolic or vascular disease are often a contraindication for a potentially curative treatment such as OLT. Careful screening and surveillance for HCC in NASH patients is mandatory, but limited by the insidious course of the disease and the lack of reliable, non-invasive diagnostic tools. The development of HCC probably stems from the contribution of cirrhosis and of the metabolic derangements associated with NASH. Diabetes and obesity have been established as independent risk factors for HCC. Insulin resistance, oxidative stress and an imbalance in adipokine/cytokine interplay, involved in the development of NASH, could also stimulate liver carcinogenesis. The future prevalence of HCC in NASH and in NASH-related cirrhosis is expected to increase with the growing epidemic of diabetes and obesity. A potential role of pharmacological therapy can be envisaged, but currently our main efforts should be directed to promote healthful dietary practices and physical activity as a cultural norm.