AIM: To investigate the regulatory ef-fects of silybin on hepatic lipid metabolism in mice with non-alcoholic steatohepatitis (NASH) induced by high -fat and high-cholesterol (HFHD) diet. METHODS: Mice were fed a HFHD diet to construct a NASH model, and serum levels of triacylglycerol (TAG), total cholesterol (T-CHO), low-density lipo-protein cholesterol (LDL-C) and high-density lipo-protein cholesterol (HDL-C) were measured using biochemical kits. H&E staining and oil red O stain-ing were used to detect histopathological changes in the liver. Lipidomics was used to detect the alter-ations of hepatic lipid metabolism in NASH mice.