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Hepatocellular carcinoma (HCC) is a major disease worldwide. There were 782,000 estimated new cases globallyin 2012 with the majority (76%) occurring in Asia, especially China. Although the etiologies are similar, the prevalence ofeach HCC risk factor varies in different geographic regions. In China, hepatitis B virus (HBV) infection is the major causeof HCC, whereas in Japan, US and Europe, hepatitis C virus (HCV) infection predominates. With the epidemic of obesityand diabetes, non-alcoholic fatty liver disease (NAFLD), especially its more aggressive form non-alcoholic steatohepatitis(NASH), has now become a major contributor to HCC. It is anticipated that NAFLD/NASH is likely to overtake viralhepatitis as the leading contributor to HCC in the future. Prior success in reducing HCC cases through hepatitis Bimmunization program and effective HBV treatments is likely to be offset by rising significance of NASH-associated HCC.In view of this, appropriate measures such as aggressive monitoring clinical course and prognoses of patients with HCCfrom NASH, studying pathogenesis and mechanism by which NASH promotes HCC, and developing novel intervention andtreatment strategy for these patients would be important to address this important public health challenge.