Nonalcoholic fatty liver disease (NAFLD) is one of the major drivers for the rising trend in hepatocellular carcinoma (HCC). Over the past three decades, the incidence of both NAFLD and HCC have increased two- to threefold. It has been forecasted that the number of patients with NAFLD in the Unites States will reach 101 million by 2030; global increase is also foreseen. This trend will likely continue to translate into increased HCC in the Unites States and across the globe. In this chapter, we summarize the current evidence linking NAFLD, metabolic syndrome, particularly obesity and type 2 diabetes mellitus, and HCC. We describe the main molecular mechanisms connecting these metabolic perturbations and hepatocarcinogenesis.