Abstract： Objective： To observe the therapeutic effect of Jiangan Xiaozhi Prescription on non-alcoholic fatty liver disease （NAFLD） model mice and its impact on ferroptosis through the glutathione peroxidase 4 （GPx4） signaling pathway. Methods：A total of 60 C57BL/6J mice were randomly selected，with 50 mice being induced to establish a NAFLD model with a high-fat diet，and the other 10 mice being treated as the normal group with a regular diet. After modeling， the mice were divided into the model group， the inhibitor group， and the Chinese medicine groups with low-，medium-，and high-doses，with 10 mice in each group. The Chinese medicine groups and the inhibitor group were given different concentrations of drugs by gavage， and the normal group and the model group were given equal volumes of 0.9% sodium chloride solution. Detected the body mass， liver index， and blood lipid indicators of each group of mice，and evaluated the therapeutic effect of Jiangan Xiaozhi Prescription on NAFLD model mice by staining liver paraffin sections with hematoxylin eosin （HE）. Evaluated the effect of Jiangan Xiaozhi Prescription on lipid peroxidation levels in NAFLD model mice by detecting the levels of malondialdehyde （MDA），4-hydroxynonenal （4- HNE）， and reactive oxygen species （ROS）. The effects of Jiangan Xiaozhi Prescription on ferroptosis and GPx4 signaling pathway in NAFLD model mice were evaluated by detecting the levels of total Ferric ions （Fe），transferrin， six transmembrane epithelial antigen of the prostate 1 （STEAP1），ferritin heavy chain 1 （FTH1），and GPx4 protein. Results： The liver plates of the normal group mice were arranged neatly and structurally normal； the liver plate arrangement of the model group mice was disordered and there was a large amount of inflammatory cell infiltration， indicating severe hepatic steatosis；the pathological relief was most significant in the inhibitor group and the high-dose Chinese medicine group. Compared with the normal group，the body mass and Fe content in the liver tissue in the model group mice were decreased （P＜0.05），while the liver indexes，ALT，AST，TG，TC，MDA，ROS，and 4-HNE levels were increased （P＜0.05）. Compared with the model group，the body mass and Fe content in the liver tissue of mice in the inhibitor group，the medium-dose Chinese medicine group，and high-dose Chinese medicine group were increased （P＜0.05）， while the liver indexes， ALT， AST， TG， TC， MDA， ROS， and 4-HNE levels were decreased （P＜0.05）. The qPCR results showed that compared with the normal group， the expression of Steap1 and Transferrin in the model group were increased， while the expression of FTH1 and GPx4 were decreased （P＜0.05）. Compared with the model group，the inhibitor group，the medium-dose Chinese medicine group，and the high-dose Chinese medicine group showed a decrease in the expression of Steap1 and Transferrin in mice，while the expression of FTH1 and GPx4 were increased （P＜0.05）. Western blotting results showed that compared with the normal group，the expression levels of Steap1 and Transferrin proteins were increased in the model group mice，while the expression levels of FTH1 and GPx4 proteins were decreased（ P＜0.05）. Compared with the model group，the expression levels of Steap1 and Transferrin proteins in the liver tissues of mice in the inhibitor group，the medium-dose Chinese medicine group， and the high-dose Chinese medicine group were decreased， while the expression levels of FTH1 and GPx4 proteins were increased （P＜0.05）. Conclusion： The Jiangan Xiaozhi Prescription may exert therapeutic effects on NAFLD model mice by regulating the GPx4 signaling pathway to inhibit ferroptosis.