Summary What is known and objectives Different population pharmacokinetics (PPK) models of tacrolimus have been established in various populations. However, the tacrolimus PPK model in paediatric systemic lupus erythematosus (PSLE) is still undefined. This study aimed to establish the tacrolimus PPK model in Chinese PSLE. Methods A total of nineteen Chinese patients with PSLE from real‐world study were characterized with nonlinear mixed‐effects modelling (NONMEM). The impact of demographic features, biological characteristics, and concomitant medications was evaluated. Model validation was assessed by bootstrap and prediction‐corrected visual predictive check (VPC). Results A one‐compartment model with first‐order absorption and elimination was determined to be the most suitable model in PSLE. The typical values of apparent oral clearance (CL/F) and the apparent volume of distribution (V/F) in the final model were 2.05 L/h and 309 L, respectively. Methylprednisolone and simvastatin were included as significant. What is new and conclusion The first validated tacrolimus PPK model in patients with PSLE is presented. The first tacrolimus population pharmacokinetics model in patients with paediatric systemic lupus erythematosus