Objective To investigate the clinical effect of sequential therapy with Geranium wilfordii ointment and hydrocortisone butyrate cream in the treatment of childhood atopic dermatitis. Methods A total of 96 children with childhood atopic dermatitis were enrolled as subjects and were divided into treatment group, control group A, and control group B using a random number table, with 32 children in each group. Three children were lost to follow-up since they were unable to attend the hospital for further consultation, two children were lost to follow-up due to local skin allergy following external application of Geranium wilfordii ointment, and 1 withdrew from treatment due to other diseases; at last, 90 children completed the study and were included in analysis, with 30 children in each group. All children were given oral administration of desloratadine syrup; in addition, the children in the treatment group were given sequential therapy with Geranium wilfordii ointment and hydrocortisone butyrate cream, those in the control group A were given external application of hydrocortisone butyrate cream twice a day, and those in the control group B were given external application of Geranium wilfordii ointment once a day. Scoring Atopic Dermatitis (SCORAD) score was used to evaluate the severity of skin lesion, the degree of pruritus, and the influence on sleep index. The children were followed up after 8 weeks to observe recurrence rate, and the incidence rates of adverse reactions were recorded. Results The three groups had a gradual reduction in SCORAD score after 2 and 4 weeks of treatment, and SCORAD score at the later time point was significantly lower than that at the earlier time point(P<0.05).After 2 weeks of treatment,the treatment group had a significantly lower SCORAD score than the control group B (P<0.05), and after 4 weeks of treatment, the treatment group had a significantly lower SCORAD score than the control groups A and B (P<0.05). The treatment group had a significantly better clinical outcome based on SCORAD score than the control groups A and B (P<0.05). There were no significant differences in the incidence rate of adverse reactions and recurrence rate between the three groups (P>0.05). Conclusion In the treatment of childhood atopic dermatitis, sequential therapy with Geranium wilfordii ointment and hydrocortisone butyrate cream can reduce the degree of skin lesion and improve clinical symptoms with good safety.