Objectives: Several genetic and non-genetic risk factors are implicated in the etiology and pathogenesis of primary immune thrombocytopenia (ITP). Protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) plays an important role in regulation of signal transduction through the T-cell receptors. PTPN22 1858 C>T single nucleotide polymorphism was reported to be associated with increased risk of autoimmune diseases. There are very few studies investigating the role of PTPN22(SNP) 1858C > T in childhood ITP. Methods: This case-control study was designed for assessing the contribution of PTPN22 1858 C>T polymorphism to the risk of ITP in Egyptian children. Eighty children with newly diagnosed ITP were recruited from pediatric hematology out-patient clinic. Also, eighty age and sex matched healthy children were enrolled as a control group. PTPN22 1858C/T SNP gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) Results: Frequency of PTPN22 1858 C/T genotypes CT, CC, and TT were 32.5,55, and 12.5% in patients versus 10, 90, and 0% in controls (p < 0.05).TT genotype was significantly associated with higher risk of ITP (OR = 17.8(0.94–333.35), 95% CI, and P = 0.02). Conclusion: PTPN22 gene polymorphism may play a pivotal role in genetic predisposition to ITP and disease progress in Egyptian children.