To analyze the application effect of whole-course nursing mode in autologous epidermal grafting for patients with vitiligo and its influence on quality of life. Methods From January 2022 to January 2023, 100 patients with vitiligo autologous epidermal grafting admitted to the Department of Dermatology, Affiliated Hospital of Guizhou Medical University were randomly divided into reference group and experimental group, with 50 patients in each group. The reference group was given routine postoperative nursing mode, and the experimental group was given whole-course nursing mode. The nursing effect, postoperative pain and quality of life were compared between the two groups. Results The total effective rate of nursing in the experimental group was 98.00%, which was higher than 84.00% in the reference group (P <0.05). The pain (NRS) score of the experimental group was lower than that of the reference group (P <0.05). The scores of quality of life (SF-36) in the experimental group were higher than those in the reference group (P <0.05). Conclusion Whole-course nursing can improve the skin state of vitiligo patients after autologous epidermal grafting, improve the recovery rate of patients, reduce pain and improve the quality of life of patients, which is worthy of application.