Metabolic reprogramming is a key characteristic of hepatocellular carcinoma, and abnormal fatty acid metabolism is closely associated with tumor immune escape. This article systematically reviews the molecular mechanisms of fatty acid metabolic reprogramming in hepatocellular carcinoma, focusing on key enzymes and their transcriptional regulatory networks within de novo lipogenesis and fatty acid oxidation pathways. This article also analyzes the metabolic heterogeneity between β-catenin-mutant hepatocellular carcinoma and AXIN1-mutant hepatocellular carcinoma and their therapeutic implications, summarizes the multidimensional mechanisms by which the lipid microenvironment regulates immune cell function, and reviews the targeted therapeutic strategies for different molecular subtypes of hepatocellular carcinoma.