Non-alcoholic fatty liver disease (NAFLD) will become a dominant cause of hepatocellular carcinoma (HCC) in the coming decade. Whereas the exact molecular mechanisms underlying the progression from simple steatosis, through steatohepatitis, to HCC remains largely unclear, emerging evidence has supported a central role of defective autophagy in the pathogenesis of NAFLD and its complications. Autophagy not only regulates lipid metabolism and insulin resistance, but also protects hepatocytes from injury and cell death. Nevertheless, in inflammation and tumorigenesis, the role of autophagy is more paradoxical. In NAFLD, defective hepatic autophagy occurs at multiple levels through numerous mechanisms and is causally linked to NAFLD-related HCC. In this chapter, we summarize the regulation and function of autophagy in NAFLD and highlight recent identification of potential pharmacological agents for restoring autophagic flux in NAFLD.