NASH (Non-alcoholic Steatohepatitis) presents a major health problem due to its high prevalence (an estimated 5–10% of the Western population suffer from NASH) and because of the increased risk of advancing into liver cirrhosis or hepatocellular carcinoma (HCC). FXR is a nuclear receptor for bile acids and upon activation it modulates various steps in bile acid, cholesterol and glucose metabolism resulting in a beneficial metabolic profile. FXR also exerts anti-apoptotic and anti-fibrotic effects that can be experimentally shown but are less well understood. We aimed in testing the effect of FXR agonists on preventing the progression of NASH and liver cirrhosis into hepatocellular carcinoma (HCC). A suitable animal model for this is the hypoinsulinemic STAM(r) mouse which progresses through all phases of metabolically induced liver disease starting with steatosis over NASH, liver cirrhosis and finally HCC. The FXR agonist Px102 when administered daily starting in week 8 ameliorated the severity of liver histopathology in animals that were sacrificed in week 16 and it reduced overall mortality and reduced tumor numers and sizes in Px-102 treated animals as opposed to vehicle treated animals. Thus using FXR agonist Px-102 for the treatment of NASH might ultimately prevent the further progression towards HCC which is the key justification for treating patients with a pharmacotherapy at NASH stage.