To explore the effect of comfortable nursing in the repair of chronic skin ulcer. Methods A total of 60 patients with chronic skin ulcers who were treated in the Second Affiliated Hospital of Anhui Medical University from March 2022 to March 2023 were selected and divided into control group and experimental group according to the random number table method, with 30 patients in each group. All patients underwent chronic skin ulcer repair. On this basis, the control group was given routine intervention, and the experimental group was given comfort nursing intervention. The nursing effect, the expression levels of TGF-β1 and EGF in granulation tissue, the skin color of medical aesthetic repair area and the satisfaction with wound healing and beauty were compared between the two groups. Results The total effective rate of the experimental group was 93.33%, which was higher than 56.67% of the control group (P <0.05). The expression levels of TGF-β1 and EGF in granulation tissue after nursing in the two groups were lower than those before nursing, and those in the experimental group were lower than those in the control group (P <0.05). The total normal rate of skin color in the repair area of the experimental group was 93.33%, which was higher than 60.00% of the control group (P <0.05). The total satisfaction rate of wound healing and cosmetology in the experimental group was 83.33%, which was higher than 60.00% in the control group (P <0.05). Conclusion Comfortable nursing intervention plays an important role in the repair of chronic skin ulcer, which can improve the nursing effect, the laboratory indexes and skin problems, and the total satisfaction of patients with wound healing is high.