Abstract: Objective: To evaluate the weight loss effect of turmeric combined with hawthorn and explore its weight loss mechanism. Methods: Thirty-two C57BL/6J mice were randomly divided into four groups: normal group, normal intervention group, high-fat group and high-fat intervention group, 8 mice in each group. The mice were gavaged with the corresponding drugs regularly every day, and the changes of adiposity, leanness, food intake and water consumption were detected regularly every week. The random blood glucose of the mice was measured at the same time every two weeks, after 12 weeks, the mice were removed from the cervical spine and the specimens were collected. The contents of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were measured in serum. The morphological changes of fat and liver tissue were observed by HE staining of epididymal fat and liver. The relative mRNA expressions of cholesterol 7α-hydroxylase (CYP7A1), fatty acid synthase (FAS), Liver X Receptorα (LXRα), Sterol Regulatory Element Binding Protein 2 (SREBP2), Sterol Regulatory Element Binding Protein (SREBP1C), Steary-coenzyme A dehydro-synthase-1 (SCD1) in liver were measured by real time polymerase chain reaction (RT-PCR). Results: Compared with the high-fat group, the body mass, fat percentage, TG, TC, LDL-C of mice in the high-fat intervention group were significantly decreased, lean meat percentage and HDL-C were significantly increased (P<0.05), and there was no significant difference in food intake and water intake. It could inhibit adipocyte hypertrophy and reduce fat deposition. And their liver cell vacuolation and inflammatory infiltration were improved. The mRNA expression level of CYP7A1 in liver was significantly increased (P<0.05). The mRNA expression levels of LXRα, SREBP1C, SCD and FAS were extremely significantly decreased (P<0.01). There was no significant change in the expression level of SREBP2 mRNA. Conclusion: Turmeric-hawthorn has good weight loss effects, and its weight loss mechanism is related to the regulation of mRNA expression levels in related genes.