Several variants involved in the expression of proteins related to immunopathological mechanisms have been associated with dengue, but few specifically related to severe dengue. In addition, children are a group with a high incidence and mortality rate due to dengue. Several immunopathological processes developed specifically in children affected with severe dengue partially explain this risk condition. This case-control retrospective study aimed to examine the association of variants in CD209, NFKBIA, IL12B, and IL1B genes with severe dengue. These genes encode proteins involved in one of the main pathways of the immune response against dengue virus infection. The study population included affected children and householding controls from Brazil. Genotyping was performed with Real-Time TaqMan assays, and the association analysis was performed with conditional logistic regressions. We found the IL1B rs1143634 genotypes carrying the T allele to be associated with susceptibility to severe dengue in children. The lower circulating levels of IL-1β associated with carrying the T allele of the IL1B rs1143634 suggest a role of this cytokine in the impairment of the immune response and plasma leakage, and, consequently, in the development of severe dengue.