Objective To analyze the application effect of comprehensive nursing intervention in patients with refractory skin diseases. Methods A total of 70 patients with refractory skin diseases admitted to our hospital from May 2021 to May 2022 were selected as the research objects and divided into reference group and analysis group according to the random number table method, with 35 cases in each group. The reference group was given routine nursing, and the analysis group was given comprehensive nursing. The improvement of negative emotions, nursing satisfaction, skin lesion score and quality of life were compared between the two groups. Results The SAS and SDS scores of the analysis group after nursing were lower than those of the reference group, and the differences were statistically significant (P