OBJECTIVE: To investigate the effect of programmed death 1 (PD-1) inhibitors combined with radiotherapy on the expression of P53 and epidermal growth factor receptor (EGFR) in breast cancer (BC). The impact of radiation treatment on BC patients' prognosis was examined. METHODS: The data of BC patients admitted to Nanjing University of Chinese Medicine from April 2022 to April 2023 were retrospectively analyzed. The clinical data of the patients were extracted, and 104 patients were randomly enrolled. The survival time and complications of patients were followed up. The expression levels of P53 and EGFR in tumor tissues and prognosis of patients treated with PD-1 inhibitor combined with radiotherapy were analyzed. RESULT: The expression level of EGFR in the joint group (JG) was visibly lower as against the control group (CG); The median progression-free survival (PFS) of the JG was visibly longer as against the CG (all P < 0.05). The optimal cut-off values of P53 positive rate and EGFR level before combined treatment were 10% and 96.21ng/mL. In addition, the median PFS of individuals with low EGFR in the JG was 7.3, which was visibly higher as against individuals with high EGFR. The level of EGFR before PD-1 inhibitor treatment was an independent cause of risk affecting the prognosis of patients. CONCLUSION: PD-1 inhibitor plus radiotherapy can effectively inhibit the expression of EGFR in tumor tissues of BC patients and visibly improve the prognosis. CLINICAL TRIAL NUMBER: Not applicable.