Interleukin 10 (IL10) is a pleiotropic cytokine that stimulates various hematopoietic cells. The tumor necrosis factor alpha (TNFα) is a cytokine that may influence the transcriptional activity induced by glucocorticoids. This study examined the impact of TNFα (G308A) and IL10 (G1082A) polymorphisms at promoter regions in relation to the overall survival of 105 children (0 ≤ 18 years) with acute lymphoblastic leukemia (ALL) for a period of 126 months, treated according to the protocol GBTLI99. The G1082A and G308A polymorphisms were identified by allele-specific PCR and PCR-RFLP, respectively. Patients with IL10AA genotype had a higher death ratio (44%, P = 0.0089). Patients with both IL10AA and TNFAA genotypes showed the worst survival when compared with the IL10GG and TNFGA genotypes (P = 0.0043). The results of this study revealed a lower survival among patients with IL10AA genotype and the concomitant occurrence of IL10AA and TNFAA genotypes.