Objective To explore the clinical effect and safety of 0.03% tacrolimus ointment combined with soothing moisturizer cream in the treatment of atopic dermatitis in children. Methods Sixty-four children with atopic dermatitis admitted to our hospital from August 30, 2020 to August 30, 2021 were selected as the research objects. They were divided into observation group and control group by random number table method, with 32 cases in each group. The control group was treated with 0.03% tacrolimus ointment and vaseline ointment. The observation group was treated with 0.03% tacrolimus ointment combined with soothing and moisturizing cream. The severity of dermatitis [atopic dermatitis (SCORAD) score], clinical efficacy, adverse reactions and recurrence were compared between the two groups. Results The SCORAD scores of the observation group were lower than those of the control group after 2 and 4 weeks of treatment (P<0.05). The total effective rate of treatment in the observation group was 93.75%, which was higher than 68.75% in the control group (P<0.05). There was no significant difference in the incidence of adverse reactions and recurrence rate between the two groups (P>0.05). Conclusion 0.03% tacrolimus ointment combined with soothing moisturizer cream is effective in the treatment of atopic dermatitis in children, which can effectively improve the clinical symptoms of children, reduce the severity of dermatitis, and will not increase the incidence of adverse reactions and recurrence rate. The safety of medication is high.