Background: Cytokines act as a potent immunomodulator. Pathogenesis of idiopathic nephrotic syndrome (INS) is associated with Th1 and Th2 cytokines imbalance. Objectives: The aim of this study is to analyse a possible association of Cytokine Gene Polymorphisms (IL4- C590T, IL6-G174C and TNFα-G308A) and response to corticosteroid therapy in children with Nephrotic Syndrome in Egypt. Materials and Methods: 90 participants were selected: 60 children with nephrotic syndrome (30 with steroid sensitive nephrotic syndrome (SSNS), 30 with steroid resistant nephrotic syndrome (SRNS) and 30 age and sex matched healthy control children. Children were analyzed for IL-4, IL-6, and TNF-α gene polymorphisms by using polymerase chain reaction and restriction fragment length polymorphism. Results: On comparing the 2 patient groups (SSNS and SRNS) the results showed that there are statistically significant difference as regards IL6-G174C for the distribution of genotypes and alleles, while as regards TNFα-G308A there is a statistically significant difference in the allele distribution only. IL4-C590T analysis showed neither statistically significant difference in the genotypes nor in the allele distribution. Conclusions: IL6-G174C and TNFα-G308A polymorphisms may affect steroid response in children with INS.