Objective To explore the application effect of comfort nursing in the nursing of skin herpes in children with handfoot- mouth disease. Methods From June to December 2022, 58 children with hand-foot-mouth disease skin herpes admitted to our hospital were selected as observation objects. They were randomly divided into control group and study group, with 29 cases in each group. The control group was given routine nursing, and the study group was given comfortable nursing. The comfort, cooperation, herpes healing index and nursing satisfaction of the two groups were compared. Results The comfort scores of the study group were higher than those of the control group, and the difference was statistically significant (P <0.05). The healing rate of herpes ulcer in the study group was higher than that in the control group, and the healing time of herpes ulcer was lower than that in the control group, the difference was statistically significant (P <0.05). The nursing satisfaction of the study group was higher than that of the control group, and the difference was statistically significant (P <0.05). The anxiety and cooperative behavior levels of the study group were better than those of the control group, and the difference was statistically significant (P <0.05). Conclusion Comfortable nursing is effective in the nursing of skin herpes in children with hand-foot-mouth disease, which can improve the comfort and cooperation of children, accelerate the healing rate of herpes ulcer, and has high nursing satisfaction. It is worthy of clinical application.