The narrow therapeutic index and large inter-individual variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring (TDM) necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with immune cytopenia. The objective of this study was to characterize the PK of sirolimus in pediatric patients with immune cytopenia and to develop a population PK model in Chinese children and evaluate its utility for dose individualization. A total of 27 children with either acquired or congenital immune cytopenia aged 8.16 ± 3.60 years (range: 1–15 years) were included. TDM data for sirolimus were collected. The population PK model of sirolimus was described using the nonlinear mixed-effects modeling (Phoenix NLME 1.3 software) approach. Covariate analysis was applied to select candidate factors associated with PK parameters. The final model was validated using bootstrap (1000 runs) and visual predictive check (VPC) method. A one-compartment model with first-order absorption and elimination was developed. The outcome parameters were as follows: apparent clearance (CL/F) 5.63 L/h, apparent distribution volume (V/F) 144.16 L. Inter-individual variabilities for CL/F and V/F were 3.53% and 7.27%, respectively. The intra-individual variability of proportional error model was 22.45%. The covariate test found that body weight and total bilirubin were strongly associated with clearance; however, we did not find the relevance between the covariate and volume of distribution of sirolimus. Personalized dosage regimens were provided based on Bayesian method. The oral dose should be adjusted according to weight and total bilirubin. This is the first study to describe a population PK model of sirolimusin pediatric patients with immune cytopenia. Population pharmacokinetic (PPK) model–based dose individualization of sirolimus and the design of future clinical studies in children will be facilitated by the developed model in this study.