Chinese children are more susceptible to the development of thiopurine-induced leukopenia compared with Caucasian populations. The aim of our study was to establish a 6-mercaptopurine (6-MP) dose-concentration-response (DCR) relationship through exploration of pharmacogenetic factors involved in the thiopurine-induced toxicities in Chinese pediatric patients afflicted by acute lymphoblastic leukemia (ALL). Blood samples were obtained from ALL children treated with 6-MP. We determined the metabolite steady-state concentrations of 6-MP in red blood cells (RBCs) by using HPLC. Pharmacogenetic analysis was carried out on patients' genomic DNA using the MassArray genotyping platform. Sixty children afflicted by ALL who received 6-MP treatment were enrolled in this study. The median concentration of 6-TGN in patients afflicted by leukopenia was 235.83 pmol/8×108 RBCs, which was significantly higher than for patients unafflicted by leukopenia (178.90 pmol/8×108 RBCs; P = 0.029). We determined the population special target 6-thioguanine (6-TGN) threshold to have equaled 197.50 pmol/8×108 RBCs to predict leukopenia risk in Chinese pediatric patients afflicted by ALL. Among 36 candidate single nucleotide polymorphisms, our results indicated that NUDT15 (rs116855232) and IMPDH1 (rs2278293) were correlated with a 5.50-fold and 5.80-fold higher risk of leukopenia, respectively. MTHFR rs1801133 variants were found to have had a 4.46-fold significantly higher risk of hepatotoxicity versus wild-type genotype. Our findings support the idea that predetermination of genotypes and monitoring of thiopurine metabolism for Chinese pediatric patients afflicted by ALL is necessary to effectively predict the efficacy of treatments and to minimize the adverse effects of 6-MP maintenance therapy. This article is protected by copyright. All rights reserved.