Objective To analyze the clinical characteristics of early death in newly diagnosed children with acute promyelocytic leukemia (APL), and to explore the direct causes of death and the risk factors leading to early death. Methods The clinical data of newly diagnosed APL children admitted from January 2013 to December 2020 were retrospectively analyzed. Results A total of 103 children with APL (56 boys and 47 girls) were included. The median age of onset was 9.0 (7.0-13.0) years old. There were 24, 41 and 38 children in low, medium and high risk groups, respectively. Early death occurred in 13 children. Compared with the survival group, the early death group had higher proportions of initial white blood cell count (WBC) ≥100×10⁹/L, prothrombin time (PT) ≥3 s, D-dimer ≥9mg/L, bone marrow promyelocytes percentage ≥90%, and high risk, and the differences were statistically significant (P<0.05). Among the 13 children who died early, 10 were boys and 3 were girls. The median time from diagnosis to death was 4.0 (2.0-7.0) days. All the 13 children died of hemorrhage, including 13 cases of intracranial hemorrhage and 5 cases of intracranial hemorrhage combined with pulmonary hemorrhage. Multivariate logistic regression analysis showed that WBC≥10×10⁹/L at first diagnosis (OR=17.27, SE=1.12, 95%CI: 1.92-155.04) was an independent risk factor for early death. Conclusions The early case fatality rate of children with APL is high, and WBC≥10×10⁹/L at first diagnosis is an important predictor of early death in children with APL.