Background: Neuroinflammation is an important feature of epileptogenesis.Objectives: To investigate the association of Interleukin-1beta-31 (IL-1β-31) and Interleukin-1 receptor antagonist (IL1-RA) genetic polymorphisms with idiopathic generalized epilepsy and demonstrate their influence on drug resistance in children.Materials and Methods: One hundred children with idiopathic generalized epilepsy were age and gender-matched with apparently healthy controls. Both groups were genotyped for IL-1β-31, and IL1-RA gene variants, analysis of these single nucleotide polymorphisms (SNPs) was done through restriction digestion of the corresponding polymerase chain reaction (PCR) products by restriction fragment length polymorphism (RFLP) assay.Results: Genotype frequency of rs1143627 TT of IL-1β-31 and the homozygous IL1RN*I were found to be more prevalent in epileptic patients (p < .05, OR 0.12 and 5.27respectively). Also observed, T allele of IL-1β-31 and IL1-RAI/I were substantially positively correlated with drug resistance against those who responded well to antiepileptic drugs (AEDs).Conclusions: The significant association with IL-1β-31T and IL1-RAN*I alleles potentiated their useful role as predictive markers for the development of epilepsy and response to medical therapy.