Lymphotoxin-α (LT-α) and interleukin-1beta (IL-1β) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-α (+252A/G) and IL-1β (+3953T/C and -511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was not found any significant differences in allele and genotype frequencies of LT-α (+252A/G) and IL-1β (+3953) among the study groups. However, the frequency of IL-1β -511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1β -511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1β CC (-511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1β -511C allele, CC genotype and CC (-511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1β -511TT genotype, T allele and TT haplotype (-511/+3953) might be counted as the influential factors for resistance to the disease.