Hemophilias are the most common X-linked inherited blood diseases that, if not properly treated, can cause lifelong debilitations. The challenges and problems in babies differ from that in older kids and adults. Blood loss conditions continue to dominate as diagnostic triggers in children, but the locations of blood loss vary with age. The TNF-α-308 gene polymorphism in children with moderate to severe hemophilia correlates with genetic background and with the clinical phenotype of the cases. This study was a case control conducted in fifty hemophilic and fifty age- and sex-matched healthy cases from September 2020 to October 2021. Results; a significant change was found among positive and negative inhibitors regarding the number of factors eight exposure days >20 days (in positive inhibitors was 59.3% compared to adverse inhibitors 27.8%). Conclusion: The (TNF-)308 gene polymorphism is significantly correlated with inhibitor progress in severe Haemophilia A cases. TNF-Alpha gene might be of use as a biomarker as well possible immune response modulator in Haemophilia A patients receiving substitute treatment. Keywords: polymorphism, TNF-α -308Haemophilia, inhibitor, prophylaxis - intracranial hemorrhage and pediatrics.