The purpose of this study is to review the recent literature on the epidemiology of NAFLD-related HCC and discuss published data on primary and secondary prevention of NAFLD-related HCC, including surveillance for HCC. Hepatocellular cancer (HCC) is the fastest rising cause of cancer-related deaths in the USA. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the USA, afflicting nearly one in three Americans and is increasingly linked to the development of HCC. NAFLD will likely become the major contributor to the burden of HCC in the USA. While cirrhosis remains the most important risk factor for HCC in NAFLD, mounting evidence indicates that NAFLD patients can rarely develop HCC in the absence of cirrhosis. While effective medical therapies for NAFLD exist, their role as chemopreventive agents against HCC is unclear. Major knowledge gaps remain in our understanding of the risk of HCC and the interplay between HCC-promoting factors in patients with NAFLD. Currently, efforts should focus on prompt diagnosis of NAFLD and cirrhosis with non-invasive methods, or liver biopsy as needed. This will identify the great majority of NAFLD patients at risk for HCC. Valid and reliable methods for identifying non-cirrhotic NAFLD patients at risk for HCC are lacking, so surveillance cannot be currently recommended in the absence of cirrhosis. Meanwhile, further studies are needed to determine the magnitude of risk and specific risk factors or biomarkers for HCC in patients with NAFLD with or without cirrhosis.