AIM: To research the regulatory effects of Butein on lipid deposition and inflammation in non-alcoholic steatohepatitis (NASH). METHODS: HepG2 cells were divided into solvent control group (1‰ dimethyl sulfoxide) and different concentration of Butein groups (1, 3, 6, 12, 25, 50 μmol/L). The survival rate of HepG2 cells were detected, the low and high concentration groups of butein were determined. HepG2 cells were divided into solvent control group (1‰ DMSO), model group (induction with 1 mmol/L free fatty acids in vitro), low and high concentration of Butein groups. After 24 hours’ cell culture in each group, expression of triglyceride (TG), lipid synthesis-related factors SREBP-1c, FAS, SCD-1, lipid oxidation-related factors PPARα, CPT1A, MLYCD, and inflammatory factors TNF-α and MCP-1 in each group were detected. The model of NASH was constructed on C57BL/6J mouse by methionine choline deficiency diet (MCD). Normal diet group (ND group), model group (MCD group), low dose (100 mg·kg-1·d-1) and high dose (200 mg·kg-1·d-1) of Butein groups were established. After 4 weeks of feeding, pathological changes of liver tissues in each group were observed, contents of liver and serum TG and TC in each group were detected, and protein expression levels of lipid synthesis-related factors SREBP-1c, FAS, SCD-1 and lipid oxidation-related factors PPARα, CPT1A,  ACOX1 and MLYCD, inflammatory factors TNF-α and MCP-1in liver tissues were detected. RESULTS: Compared with solvent control group, Butein inhibited HepG2 cell growth when the concentration was ≥12 μmol/L (P<0.05). Make 5 and 10 μmol/L as low and high concentration groups, respectively. Compared with the solvent control group, the intracellular TG content of HepG2 cells in butein group was significantly lower (P<0.05). Compared with the model group, mRNA expressions of SREBP-1c, FAS, and SCD-1 was significantly lower (P<0.05), while mRNA expression of PPARα, CPT1A, and MLYCD was significantly higher (P<0.05), mRNA expression of TNF-α, MCP-1 was significantly decreased (P<0.05) in high-concentration butein group. Compared with the model group, the expression of SREBP-1c, FAS, SCD-1, MCP-1, TNF-α protein decreased and the expression of PPARα, CPT1A, MLYCD protein increased in the high concentration group. Compared with ND group, liver histological sections of MCD group showed obvious fat accumulation and inflammatory cell infiltration. Compared with the MCD group, the pathological manifestations of fat accumulation and inflammatory cell infiltration in the liver tissue of the butein groups were significantly improved, and the contents of TG and TC in the liver tissue of the butein groups were significantly decreased (P<0.05), while the protein expressions of PPARα, CPT1A, ACOX1, MLYCD were increased, and the protein expressions of SREBP-1c, FAS, SCD-1, TNF-α and MCP-1 were decreased in butein groups. CONCLUSION: Butein can improve lipid deposition and inflammation in NASH livers. Its mechanism may be to reduce the expression of lipid synthesis-related factors, enhance the expression of lipid oxidation-related factors, and reduce the expression level of inflammatory factors.