To investigate the genetic contribution of 24 GWAS-associated polymorphic gene variants on the development of children's B-lineage acute lymphoblastic leukemia (B-ALL) in an ethnically homogeneous population of Kazakhs. A study of 205 children with B-ALL and 204 healthy children was conducted. Genotyping of polymorphic loci was carried out using the TaqMan method. Significant associations (p < 0.05) with the risk of childhood B-ALL were found for twelve variants, including rs6457327 of the HLA gene, rs4251961 of the IL1RN gene, and rs1800630 of the TNF gene. Carriage of the minor allele A of the protective rs1801157 polymorphism A of the CXCL12 gene reduces the risk of B-ALL in the Kazakh population by 40%. The results reveal significant associations of polymorphic genetic variants, which can serve as a basis for the development of effective methods for predicting the risk of B-ALL, early diagnosis, and timely treatment.