Objective To summarize the clinical features of anti-melanoma differentiation-associated gene 5 antibody (MDA5)-positive juvenile dermatomyositis (JDM), and to study its treatment and evaluation. Methods The basic information, clinical manifestations, laboratory and imaging examinations, treatment and prognosis of 5 children with anti-MDA5-positive JDM who were hospitalized from January 2019 to May 2022 were retrospectively analyzed. Results All 5 patients (3 boys and 2 girls) had typical Gottron rash/sign, 3 had skin ulcer, 2 had skin calcification, and 1 had digital necrosis. All the 5 patients had normal muscle strength, but abnormal muscle MRI. Myositis specific antibodies were positive for anti-MDA5 antibodies in all children, and 3 patients were positive for anti-Ro-52. All 5 patients showed interstitial lung disease on high-resolution CT. Only 1 patient had shortness of breath, 2 had elevated KL-6, and 2 had digestive tract involvement. All 5 patients were treated with corticosteroids, and 4 were treated with cyclophosphamide as the initial immunosuppressant, and all of them were partially relieved within 2 months. Conclusions The onset age of anti-MDA5-related JDM is relatively low, the clinical manifestations are primarily typical rash, muscle involvement is not evident, primarily clinically amyopathic dermatomyositis, and the incidence of interstitial lung disease is high. Anti-MDA5 antibody titer, high-resolution CT, KL-6 examination is particularly important for diagnosis and evaluation of disease efficacy. The main treatment is methylprednisolone combined with immunosuppressive agents. The combined treatment with tofaciib is effective.