Fig. 1. The potential roles of xenobiotics in non-alcoholic fatty liver diseases. Abbreviations: NAFL, non-alcoholic fatty liver; NASH, non-alcoholic steatohepatitis; HCC, hepatocellular carcinoma; NR, nuclear receptor; ER, endoplasmic reticulum; % prevalence/incidence; missing value (“?”), the magnitude of non-cirrhotic liver cancer developed from NASH is not well-defined. NAFLD consists of a wide spectrum of liver damages from simple steatosis (NAFL), to steatohepatitis (NASH), fibrosis and cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multi-factorial. Genetic background, dietary factors, gut microbiota and other factors act simultaneously in the initiation and progression of NAFLD. In addition, recently studies have shown the link between xenobiotics and the courses of NAFLD. Liver is the major organ for the metabolism and transportation of drugs and environmental agents. Exposure to these compounds may lead to the lipid accumulation in the liver possibly through increased fatty acid biosynthesis, mitochondrial dysfunction, modulation of nuclear receptors, insulin resistance, and impaired lipid excretion. Moreover, the progression of steatohepatitis from simple steatosis may be induced by xenobiotics via oxidative stress, inflammation, ER stress, and cell death. Finally, chemical exposure may stimulate the cell growth in the liver, which further increases the chance of developing HCC in NAFLD.