Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease mediated by antiplatelet autoantibodies that cause platelet destruction and suppression of platelet production. Tumor necrosis factor alpha (TNF-α) is a multifunctional cytokine and is involved in the promotion of inflammatory responses. It also plays critical roles in the pathogenesis of autoimmune diseases. Objective: To assess the level of TNF-α in children with primary ITP and its contribution to pathogenesis of the disease. Patients and Methods: A case control study was conducted on 21 ITP patients (13 males and 8 females) and twenty age- and sex-matched healthy children as a control group at the Outpatient Clinic of Hematology Unit of Pediatric Department and Clinical Pathology Department at Zagazig University Hospitals, Sharkya, Egypt in the period from November 2019 to April 2020. All patients and control were subjected to full medical history, thorough clinical examination and laboratory investigations in the form of complete blood picture, PT, PTT, C3, ANA, anti-DNase and serum TNF-α by ELISA kit. Results: There was statistically significant higher serum TNF- α in ITP cases than controls with highest level in the newly diagnosed ITP cases followed by persistent then chronic cases. TNF alpha showed statistically significant negative correlation with platelets count and disease duration and positive correlation with WBCs and response to treatment. Conclusion: Significant differences in TNF alpha levels between ITP patients and healthy controls indicates that TNF alpha disturbances might be involved in the pathogenesis of ITP in pediatric patients.