Objective To explore the application effect of comprehensive nursing intervention in neonatal eczema nursing. Methods A total of 60 children with eczema admitted to the Department of Neonatology, Anhui Province Maternal and Child Health Hospital from January 2022 to January 2023 were selected as the research objects. According to the random number table method, they were divided into control group and observation group, with 30 children in each group. The control group carried out routine intervention, and the observation group carried out comprehensive nursing intervention. The recovery time of eczema symptoms, quality of life, incidence of infection events and family satisfaction were compared between the two groups. Results The eczema regression time, eczema scab time and skin itching regression time in the observation group were shorter than those in the control group (P<0.05). After intervention, the scores of itching and scratching, sleep quality, feeding status and emotional impact in the observation group were lower than those in the control group(P<0.05). The incidence of infection events in the observation group was lower than that in the control group, and the family satisfaction was higher than that in the control group (P<0.05). Conclusion The application of comprehensive nursing intervention in the nursing of neonatal eczema is effective, which can effectively shorten the time of eczema symptoms regression, reduce itching and other discomfort, improve the quality of life, reduce the rate of infection events, and improve the satisfaction of family members.