Objective To explore the relationship between the expression of human epidermal growth factor receptor-2 (HER-2), estrogen receptor (ER), phosphatase and tensin homology deleted on chromosome ten (PTEN) in breast cancer tissue and clinicopathological characteristics, as well as the prognosis of patients. Methods The clinical data of 225 female breast cancer patients admitted to Linfen Central Hospital from January 2018 to January 2022 were retrospectively analyzed, adjacent normal tissues and the invasive ductal carcinoma tissues were collected, and divided into the normal group and the cancerous group, the expression of HER-2, ER and PTEN and their relationship with clinicopathological features were tested and compared between the two groups; after 1 year of follow-up, the patients were divided into the survival group (202 cases) and the death group (23 cases) based on prognosis results, and the expression of HER-2, ER, and PTEN were compared between the normal group and the cancerous group; univariate analysis and multivariate Logistic regression analysis were performed on the data of the survival group and the death group in order to screen out independent risk factors affecting prognosis. Results The positive expression rate of HER-2 and ER and the negative expression rate of PTEN in the cancerous group were higher than those in the normal group; the proportion of patients with histological grading of 3 grade, TNM stage of Ⅲ + Ⅳ, nerve or vascular invasion and lymph node metastasisamong the patients with HER-2, ER positive expression were higher than patients with HER-2, ER negative expression; the proportion of patients with histological grading of 3 grade, TNM stage of Ⅲ + Ⅳ, nerve or vascular invasion and lymph node metastasis among the patients with HER-2, ER positive expression were lower than patients with HER-2, ER negative expression; compared with patients in the survival group, the proportion of patients with histological grade 3 grade, TNM stage Ⅲ + Ⅳ , nerve or vascular invasion, lymph node metastasis, HER-2 positive expression, ER positive expression and PTEN negative expression were higher in the death group (all P<0.05); the results of multivariate nonconditional Logistic regression model analysis showed that, histological grade 3 grade, TNM stage Ⅲ + Ⅳ , nerve or vascular invasion, lymph node metastasis, HER-2 positive expression, ER positive expression and PTEN negative expression were all the risk factors for the prognosis of breast cancer patients (OR=1.672, 1.863, 1.866, 1.548, 1.471, 1.704, 1.525, all P<0.05). Conclusion HER-2, ER were highly expressed in breast cancer tissues and PTEN was low expression in breast cancer tissues, histological grade 3, TNM stage Ⅲ+Ⅳ, nerve/vessel invasion, lymph node metastasis, HER-2 positive expression, ER positive expression, and PTEN negative expression are all the risk factors for the prognosis of breast cancer patients, detection of HER-2, ER, and PTEN expression in tumor tissues has important clinical value for the treatment and prognosis of breast cancer patients.