Objective To explore the clinical effect of autologous fat grafting combined with silicone gel prosthesis implantation for breast reconstruction after modified radical mastectomy for breast cancer. Methods A total of 48 patients who underwent breast reconstruction after modified radical mastectomy admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences from June 2023 to June 2025 were selected. According to different reconstruction methods, they were divided into the reference group and the study group, with 24 patients in each group. The reference group received silicone gel prosthesis implantation alone, and the study group received autologous fat grafting combined with silicone gel prosthesis implantation. The breast aesthetic effect, capsular contracture rate and satisfaction were compared between the two groups. Results The scores of each dimension of Harris breast aesthetics and total score in the study group were higher than those in the reference group (P <0.05). The incidence of capsular contracture in the study group at 6 months after treatment was 4.17%, which was lower than 25.00% in the reference group (P <0.05). All dimension scores of BREAST-Q and overall satisfaction in the study group were higher than those in the reference group (P <0.05). Conclusion Autologous fat grafting combined with silicone gel prosthesis implantation for breast reconstruction after modified radical mastectomy can effectively improve breast aesthetic effect, reduce the incidence of capsular contracture, and improve patient satisfaction, which possesses favorable clinical application value.