: There are strong associations between candidate genetic polymorphisms associated with intrahepatocyte lipid droplet accumulation and the development of cirrhosis, via a common sequence in which lipid accumulation is followed by chronic inflammatory injury and fibrogenesis. Hepatocellular carcinoma (HCC) has also been linked to genetic polymorphisms associated with intracellular lipid trafficking, although, as shown in the present study, not all the candidate polymorphisms implicated in fibrogenesis are also tied to HCC. Genetic analysis may identify at-risk persons who would most benefit from modifying life-style factors linked to cirrhosis and HCC, and also persons most likely to benefit from HCC surveillance.