Objective To explore the mechanism of Huayu Qutan Fomula（化瘀祛痰方） in treating atherosclerosis（AS）. Method A total of 24 ApoE

-/-

mice were randomly divided into a model group

a Huayu Qutan Fomula group

and a simvastatin group. Eight C57 BL/6 J mice were used as the blank group. Except for the blank group

mice were given high-fat feed to make AS models. The mice in Huayu Qutan Fomula group was given Huayu Qutan Fomula 20 g/（kg·d） by gavage; the simvastatin group was given simvastatin 2.275 mg/（kg·d） by gavage

and the blank group and the model group were given 0.5 ml normal saline by gavage. After intragastric administration for 4 weeks

serum triglycerides（TG）

total cholesterol（TC）

high-density lipoprotein cholesterol（HDL-C） and low-density lipoprotein cholesterol（LDL-C）

superoxide dismutation（SOD） activity

malondialdehyde（MDA）

reactive oxygen species（ROS） levels

liver ferroptosis related factor p53

glutathione peroxidase 4（GPX4）

cystine/glutamate reverse transport Body（xCT） protein and mRNA expression were detected; and the morphological changes of liver tissue were observed. Results Compared with the blank group

the levels of serum TC

TG and LDL-C in the model group were significantly increased; the levels of ROS and MDA in the liver tissue were significantly increased; SOD activity was significantly decreased; the expression of p53 protein and mRNA in the liver tissue was increased; the levels of GPX4

xCT protein and mRNA were significantly reduced（P

<

0.01）. HE staining showed that hepatocytes were swollen and the cytoplasm contained a large amount of fatty vacuoles. Compared with the model group

the serum TC

TG and LDL-C levels of the mice in the Huayu Qutan Fomula group and simvastatin group were significantly reduced; the levels of ROS and MDA in the liver tissue were significantly reduced; SOD activity was significantly increased; the levels of p53 protein and mRNA expression decreased; the levels of GPX4

xCT protein and mRNA increased significantly（P

<

0.05 or P

<

0.01）; the morphology of liver cells recovered or partially recovered

and the lipid droplet content in the cytoplasm was significantly reduced. Conclusion Huayu Qutan Fomula affects ferroptosis in liver cells by p53/xCT pathways and alleviate the lipid peroxidation injury of ApoE

-/-

mice and prevents atherosclerosis.