Objective To investigate the effect of desonide cream combined with Chushi Zhiyang ointment in the treatment of children with eczema. Methods A total of 86 children with eczema admitted to our hospital from July 2022 to June 2023 were selected as the research objects. According to the random number table method, they were divided into control group (n =43) and study group (n =43). The control group was treated with desonide cream, and the study group was treated with desonide cream combined with Chushi Zhiyang ointment. The clinical efficacy, eczema sign score, disappearance time of clinical symptoms, inflammatory factor and incidence of adverse reactions were compared between the two groups. Results The total effective rate of treatment in the study group was 95.35%, which was higher than 79.07% of the control group (P<0.05). After treatment, the scores of infiltration hypertrophy, lichenification, scratches and erythema in the study group were lower than those in the control group (P<0.05). The disappearance time of pruritus, erythema and papules in the study group was shorter than that in the control group (P<0.05). The levels of IgE, IL-2, IFN-γ and eosinophils in the study group were lower than those in the control group (P <0.05). The incidence of adverse reactions in the study group was 2.33%, which was lower than 16.28% in the control group (P <0.05). Conclusion For children with eczema, desonide cream combined with Chushi Zhiyang ointment can improve the clinical efficacy, improve the signs of eczema, accelerate the relief of clinical symptoms, reduce the level of inflammatory factors and incidence of adverse reactions.