Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers world-wide. In developed countries, the past three decades has seen the incidence of HCC treble and become the fastest rising cause of cancer related deaths. Of note, in the developed world, most HCC patients who are not hepatitis C virus positive, present with obesity and symptoms associated with the metabolic syndrome, including non alcoholic fatty liver disease (NAFLD) and non alcoholic steatohepatitis (NASH). Accordingly, the association of both obesity and NAFLD/NASH with HCC has become the focus of intense research, particularly given that current treatments for HCC are suboptimal. Liver resections and/or transplantations are treatment options, but few HCC patients can benefit from surgery because majority of patients are diagnosed at late stage. The only drug available for HCC is Sorafenib, a tyrosine kinase inhibitor that can only increase survival time by ~3 months. Insulin sensitizing drugs such as Metformin and thiazolidinediones have been shown to be effective in treating NAFLD, although the extent to which these drugs may reduce HCC in individuals with NASH is unclear. Clearly, therefore, while NASH driven HCC is growing at an alarming rate, the disease presents a clinical unmet need. In this presentation, new therapeutic strategies for the treatment of liver inflammation, NASH and HCC will be discussed.