〔Abstract〕 Objective To investigate the function and mechanism of golgi protein 73(GP73) neutralizing antibody in Methionine-choline deficient(MCD) diet-induced non-alcoholic fatty liver disease(NAFLD). Methods Total cholesterol(TC),aspartate aminotransferase(AST),triglyceride(TG) and serum alanine aminotransferase(ALT) levels were detected after MCD diet and GP73 neutralizing antibody intervention. Lipid deposition in liver tissue was observed by oil red O staining; qRT-PCR was used to detect the gene expression ofACC1,HMGR,TIMP1andTGF-βin liver tissue; Western blotting was used to detect α-SMA and SREBP1 protein expression levels in liver tissues. Results GP73 neutralizing antibody could reduce the accumulation of serum ALT and AST(P<0.001) induced by MCD diet, and increase the levels of serum TG and TC(P<0.001);The gene expression levels ofHGMR(P<0.001),TGF-β(P<0.05),ACC1(P<0.01) and the protein expression levels of α-SMA(P<0.05) and SREBP1(P<0.05) in liver tissue significantly decreased, and the lipid deposition was also improved. Conclusion GP73 neutralizing antibody inhibits the formation of MCD-induced NAFLD by slowing down the progression of liver fibrosis and reducing the deposition of liver lipids.