To investigate the association between single nucleotide polymorphism of NUDT15 gene (SNP rs116855232) and hepatotoxicity in children with acute lymphocytic leukemia (ALL). A total of 135 children with ALL in Shandong Province were recruited in this study, and patients were divided into two groups based on the presence of liver injury. Genotypes of each patient were detected using PCR and Sanger sequencing. Clinical data and the average dose of 6-mercaptopurine (6-MP) were collected and analyzed by SPSS 19.0 software. Respectively, 99 patients were found with CC genotype, 32 patients with CT genotype and 4 patients with TT genotype. Compared with ALL patients without hepatotoxicity, there was a difference in genotypes between the two groups in the initial stage of chemotherapy for leukemia (Chi = 7.583, P = 0.023). In maintenance therapy stage there was also a difference between the two groups (Chi = 10.591, P = 0.005), and T allele was a risk factor for hepatotoxicity. The polymorphism of rs116855232 in NUDT