Objective ·To investigate the clinical efficacy and safety of topical narrow-band ultraviolet B (NB-UVB) combined with desonide cream in the treatment of moderate-to-severe atopic dermatitis (AD) in children and to provide an optimized regimen for clinical practice. Methods ·A total of 166 children with moderate-to-severe AD admitted to the Department of Dermatology, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine and its Guizhou Branch were enrolled. They were divided into an experimental group (86 cases) and a control group (80 cases) according to different treatment regimens. The control group was treated with topical desonide cream combined with basic emollient therapy, while the experimental group received additional topical NB-UVB irradiation on the basis of the control group′s regimen (twice weekly, initial dose of 0.2 J/cm², adjusted as needed). The SCORing Atopic Dermatitis (SCORAD) index and Visual Analogue Scale for Pruritus (VAS) scores of the two groups were compared after 2 and 4 weeks of treatment, as well as the recurrence rate during the 8-week follow-up and the incidence of adverse reactions during treatment. Results ·After 4 weeks of treatment, both SCORAD and VAS scores in the experimental group were significantly lower than those in the control group (P<0.001, P=0.017); the total effective rate of the experimental group was 90.7% (78/86), which was significantly higher than that of the control group [76.3% (61/80); χ²=6.210, P=0.012]. During the 8-week follow-up, the recurrence rate in the experimental group was 11.5% (9/78), which was lower than that in the control group [24.6% (15/61); χ²=4.082, P=0.043]. The incidence of adverse reactions in the experimental group was 7.0% (6/86), mainly mild erythema and hypopigmentation, whereas that in the control group was 3.8% (3/80), mainly folliculitis and hypopigmentation. There was no statistically significant difference between the two groups, and no severe adverse reactions occurred in either group. Conclusion ·Topical NB-UVB combined with desonide cream has a definite efficacy in the treatment of moderate-to-severe AD in children. It can rapidly resolve skin lesions and alleviate pruritus, significantly reduce the recurrence rate, and does not increase the risk of severe adverse reactions. It provides a better option for the clinical treatment of moderate-to-severe AD in children, and is worthy of wide clinical promotion and application.