Objective To study the effect of comprehensive nursing on patients undergoing breast filling with autologous free dermal fat graft after radical mastectomy and its influence on breast aesthetics. Methods From September 2020 to July 2023, 74 patients who needed to receive breast filling with abdominal free dermal fat flap after radical mastectomy for breast cancer in Dongming County People's Hospital were randomly divided into control group and experimental group, with 37 patients in each group. The control group was given routine nursing, and the experimental group was given comprehensive nursing. The incidence of complications, adverse emotions, pain degree, breast aesthetics and nursing satisfaction were compared between the two groups. Results The incidence of complications in the experimental group was 8.11%, which was lower than 27.03% in the control group (P <0.05). The HAMA score and HAMD score of the experimental group after nursing were lower than those of the control group (P <0.05). The VAS score of the experimental group was lower than that of the control group, and the breast aesthetics score and nursing satisfaction score were higher than those of the control group (P <0.05). Conclusion Comprehensive nursing has a definite application effect in patients undergoing breast filling with autologous free dermal fat graft after radical mastectomy, which can effectively prevent postoperative complications, reduce patients' adverse emotions and pain, improve breast aesthetics, and have higher nursing satisfaction.