•Background: Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder caused by the production of anti-platelet antibodies. These autoantibodies opsonize platelets for splenic clearance, resulting in low levels of circulating platelets.Aim:The current case-control study aimed at detecting the frequency of IL-4 (VNTR intron 3) and IL-10 (-627) genes polymorphism in Egyptian children with ITP as genetic markers for ITP risk, and to clear out their possible role in the pathogenesis of ITP.•Materials and Methods:IL-4 (VNTR intron 3) and IL-10 (-627) genes polymorphisms were studied in 70 ITP patients and 50 healthy controls by PCR amplification of the target gene followed by allele specific restriction enzyme digestion (RFLP technique). Odds ratios (ORs) along with their 95% confidence intervals (CIs) were computed to compare the distribution of alleles and genotypes between cases and controls.•Results:More frequent IL-4 RP2 allele and IL-10 A allele among ITP patients than controls. A statistical significant difference between acute and chronic ITP patients as regard IL-10 and IL-4 gene polymorphism distribution with higher A allele and RP2 allele among chronic ITP patients versus acute ITP patients.Furthermore, combined polymorphism of IL-4 and IL-10 genes was associated with much more increased risk of ITP development.•Conclusion: Our study suggests the possibility that IL-4 and IL-10 genes polymorphism may contribute to the susceptibility of development of ITP in Egyptian children.