〔Abstract〕 Objective To explore the relationship between the positive expression of p53 and B-cell lymphoblastoma/ leukemia-2 (Bcl-2) genes and the clinical characteristics of breast cancer patients. Methods 120 breast cancer patients admitted to Fengcheng People's Hospital from August 2019 to July 2021 were selected. All patients were tested for p53 and Bcl-2 gene positive expression. The influencing factors of p53 and Bcl-2 gene positive expression in breast cancer patients were analyzed, and the related factors were analyzed by logistic regression analysis. Results Of the 120 patients, 85 cases were positive for p53 gene expression and 35 cases were positive for Bcl-2 gene expression. Among the patients with positive expression of p53 gene, there were significant differences in the proportion of patients with different tumor node metastasis classification (TNM) stages, tissue differentiation and estrogen receptor (ER) expression (P < 0.05). Among the patients with positive expression of Bcl-2 gene, there were significant differences in the proportion of patients with different TNM stages and histological differentiation degrees (P < 0.05). Logistic regression analysis showed that TNM stage Ⅱ-Ⅲ, low and moderate differentiation of tumor tissue, and ER positive were independent risk factors for p53 gene positive expression (P < 0.05). TNM stage Ⅱ-Ⅲ, low and moderate differentiation of tumor tissue were independent risk factors for Bcl-2 gene positive expression (P < 0.05). Conclusion The change of p53 positive expression indicates a poor prognosis of breast cancer patients. TNM stage, histological differentiation and the nature of ER can significantly affect the change of p53 positive expression rate. Bcl-2 reflects the prognosis of patients, TNM stage and tissue differentiation degree are independent risk factors for bcl-2 gene positive expression, so the determination of p53 and Bcl-2 gene positive expression can better evaluate the patient's condition and prognosis, and provide more reliable diagnostic basis for clinical diagnosis and treatment.