Abstract: Objective To summarize the clinical characteristics, laboratory findings and prognosis of patients with Down syndrome-related acute leukemia (DS-AL). Methods The clinical data, laboratory findings, chemotherapy and prognosis of 21 children with DS-AL were analyzed. Results Most of the children had disease onset of leukemia at 1 to 5 years of age (85.7%), and acute myeloid leukemia accounted for 57.1% of these cases; 61.9% of the patients had increased lactate dehydrogenase level by 2 folds or more. Of the 13 cases undergoing echocardiaography, 10 (67.9%) showed abnormal findings, and complex congenital heart disease was common (38.5% ). Six of the children received chemotherapy and complete remission was achieved in 4 cases; 2 patients died of infection, and the treatment-related mortality was 33.3%. The 2 patients receiving reduced intensive chemotherapy have so far had event-free survival for 21 and 43 months. Conclusion Acute myeloid leukemia is the most common subtype of DS-AL. Patients with DS-AL are sensitive to chemotherapy and the prognosis was favorable with reduced intensive chemotherapy.