Abstract: Objective: Autoimmune lymphoproliferative syndrome(ALPS) usually presents in childhood with fever, nonmalignant splenomegaly and lymphadenopathy along with cytopenia. Glucocorticoids, as a traditional therapeutic application of ALPS, will affect the growth of children. Sirolimus has become a new treatment option which accurately inhibit the mTOR pathway and induce T cell apoptosis, but its safety and effectiveness data in pediatrics still need to be investigated. This article aims to provide safety and effectiveness data for the application of sirolimus in the childhood ALPS with hemocytopenia in our center.Methods: This study was a single-center, retrospective cohort study, collected from 2016 to present, 12 pediatric ALPS with immune cytopenia diagnosed and treated with sirolimus for more than 1 year. The data of effectiveness and safety was evaluated.Results: The median age of the 12 children was 3.5(1-10) years old, and the median course of disease was 10 months(1 month to 3 years). Twelve cases(100%) all had immune thrombocytopenia: 7 cases(58.33%) had pancytopenia, 4 cases(33.33%) involved two lines hemocytopenia, and 1 case(8.33%) only had immune thrombocytopenia. Twelve cases(100%) had moderate or higher splenomegaly(3 cases reached degree Ⅲ), and 11 cases(91.67%) had lymphadenopathy. Efficacy:①After 3 months of treatment, 12 cases(100%) achieved remission of cytopenia, and 9 cases(75.00%) achieved complete remission. Ten cases(83.33%) achieved remission of lymphoid tissue proliferation, and 3 cases(25.00%) achieved complete remission.②At 12 months of treatment, 12 cases(100%) achieved remission of cytopenia, and 11 cases(91.67%) achieved complete remission. Twelve cases(100%) achieved remission of lymphoid tissue proliferation, and 8 cases(66.67%) achieved complete remission.③The median time to complete remission of hemacytopenia was 3 weeks(1-50 weeks), which was shorter than that of lymphatic proliferation.④Relation factors: All the children with ALPS-FAS and ALPS-FASLG mutations achieved hematologic remission at 3 months, which was earlier than other children with ALPS. The rate of double negative T cell at the beginning of the disease was significantly elevated in patients who achieved complete remission after 3 months and 6 months treatment. Safety: One case had transient elevation of glutamic pyruvic transaminase, 2 cases had oral ulcers, and no children had secondary infection due to application of sirolimus.Conclusion: Sirolimus treatment of childhood ALPS complicated with hemocytopenia has rapid response and high remission rate. After 12 months of treatment, the overall response rate of hemocytopenia and lymphatic proliferation is 100%(91.67% complete remission rate of hemocytopenia and 66.67% complete remission rate of lymphatic proliferation). The remission of hemocytopenia in children is earlier than that of lymphoproliferation. ALPS-FAS and ALPS-FASLG mutation and the significant increase in the proportion of double negative T cell before medication may be a predictor of faster complete remission.The adverse events of sirolimus are mild and tolerable. This study suggests that sirolimus is expected to be the first choice for the treatment of children with ALPS diagnosed with immune cytopenia.