Previous studies have revealed the important contribution of the immune response and oxidative stress to the development of anti-tuberculosis drug-induced hepatotoxicity (ATDH). To investigate whether single-nucleotide polymorphisms (SNPs) of the cytokine gene interleukin-6 (IL6) and oxidative stress genes xanthine dehydrogenase/oxidase (XO) and inducible nitric oxide synthase (NOS2) were associated with susceptibility to ATDH, we performed a case-control study including 41 ATDH cases and 116 ATDH-free controls in Chinese Han children. Significant difference in the allele distribution of rs1800796 in the IL6 gene was observed between the case and control groups, and the G allele of rs1800796 was associated with an increased risk for ATDH (odds ratio: 2.48, 95%CI: 1.40–4.40, P = 0.002). However, no significant difference was observed in the allele and genotype distributions of the other SNPs of the IL6, XO and NOS2 genes between the case and control groups after Bonferroni correction. In addition, no interaction was found between all selected SNPs. These findings indicate that genetic variants of the IL6 gene might contribute to the development of ATDH in the Chinese Han pediatric population.