Objective To analyze the preventive effect of comprehensive nursing intervention on eyelid ectropion in the repair of periorbital soft tissue defect with expanded flap. Methods A total of 60 patients with periorbital soft tissue defects admitted to Zunyi Bozhou District People's Hospital from February 2022 to February 2023 were selected as the research objects. All patients were treated with expanded flap repair. According to the different methods of prevention and intervention of ectropion, they were divided into control group and observation group, with 30 patients in each group. The control group was treated with routine nursing measures, and the observation group was treated with perioperative comprehensive preventive intervention. The nursing effect, nursing satisfaction and complications were compared between the two groups. Results There was no significant difference in the total effective rate of nursing between the two groups (P>0.05). The satisfaction scores of aesthetics, service attitude and service mode in the observation group were higher than those in the control group, and the differences were statistically significant (P<0.05). The incidence of complications in the observation group was 0, which was lower than 16.67% in the control group, and the difference was statistically significant (P<0.05). Conclusion Comprehensive nursing intervention has a good clinical effect in patients with periorbital soft tissue defects treated with expanded flap repair, which can reduce the occurrence of complications such as eyelid ectropion and improve patients' satisfaction with treatment and nursing.