【Abstract】Objective To study the core behavioral symptoms, biological indicators and pathological changes of the mouse model construction of breast cancer complicated with depression induced by using method of 4T1 breast cancer cell line inoculation combined with chronic restraint stress (CRS). Methods BABL/c mice were randomly divided into control group, stress group, tumor group and stress combined with tumor group (S T). 4T1 cell lines were inoculated into the underarm of mice in tumor and S T groups. After tumor formation, mice in the stress and S T groups were subjected to CRS for 21 days. Body weight and food intake of each group were monitored during modeling. After the experiment, depression-like behavior of mice in each group was evaluated by sucrose preference test, open field test, elevated plus-maze test, and forced swimming test. After the mice were decapitated, the weight and volume of mouse tumor were measured. Serum tumor markers including carbohydrate antigen (CA199), carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF) and related neurotransmitters including 5-hydroxytryptamine (5-HT), norepinephrine (NE) and corticosterone (CORT) were determined by using Elisa method. HE staining was used to observe the histopathological changes of hippocampus and tumor of mice. Results In mice of S T group, the body weight and food intake were significantly decreased, tumor weight and volume were significantly increased, serum tumor markers (CA199, CEA, VEGF) levels were significantly increased, pleasure and desire to explore the new environment were weakened, stress and despair behaviors were significantly increased, serum neurotransmitters 5-HT and NE levels were significantly decreased, and CORT levels were significantly increased. In addition, the cell arrangement of tumor tissue was loose, the interstitial was reduced, the pathological nuclear classification phase was increased, the arrangement and morphology of neurons in the CA3 region of hippocampus were disordered, and the nuclear vacuolation-like changes were obvious. Conclusion The mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell line inoculation combined with chronic restraint stress showed the dual typical symptoms and biological indicators of breast cancer and depression, which can provide a good model reference for the experimental study of breast cancer complicated with depression.