Objective To explore the effect of comprehensive holistic nursing intervention on patients with burn plastic skin grafting after operation. Methods A total of 80 patients with burn plastic skin grafting who were treated in the First Affiliated Hospital of Anhui Medical University from May 2023 to May 2024 were randomly divided into control group and experimental group, with 40 patients in each group. The control group was given routine nursing, and the experimental group was given comprehensive holistic nursing. The pain of the donor site, the recovery time of the thin split-thickness graft, the psychological status, complications, and the nursing satisfaction were compared between the two groups. Results The VAS score of donor site in the experimental group was (2.11±1.25) scores, which was lower than (4.85±1.52) scores in the control group (P <0.05). The healing time of thin split-thickness graft in the experimental group was (7.25±1.56) d, which was shorter than (9.25±1.50) d in the control group (P <0.05). The SAS score and SDS score of the experimental group were lower than those of the control group (P <0.05). The incidence of complications in the experimental group was 7.50%, which was lower than 25.00% in the control group (P <0.05). The nursing satisfaction of the experimental group was 97.50%, which was higher than 80.00% of the control group (P <0.05). Conclusion Comprehensive holistic nursing intervention after burn plastic skin grafting is beneficial to promote the recovery of donor site, accelerate the healing time of thin split-thickness graft and reduce the incidence of complications.