BackgroundPrimary immune thrombocytopenia (ITP) is a common autoimmune disorder. Secretion of TNF-α, TNF-β and IFN-γ plays a major role in the pathogenesis of ITP.ObjectiveThis cross-sectional study aimed to detect TNF-α (−308 G/A) and TNF-β (+ 252 A/G) gene polymorphism in a cohort of Egyptian children with chronic ITP (cITP) to clarify their possible association with progression to chronic disease.MethodsThe study included 80 Egyptian cITP patients and 100 unrelated age- and sex-matched controls. Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP).ResultsPatients with TNF-α homozygous (A/A) genotype had significantly higher mean age, longer disease duration and lower platelet counts (pvalues 0.005, 0.024 and 0.008, respectively). TNF-α wild (G/G) genotype was significantly more frequent among responders (p= 0.049). Complete response was more frequent among wild (A/A) TNF-β genotype patients (p= 0.011), and platelet count was significantly lower among homozygous (G/G) genotype (p= 0.018) patients. Combined polymorphisms were strongly associated with susceptibility to chronic ITP.ConclusionHomozygosity in either gene might contribute to a worse course of disease, increased severity and poor response to therapy. Patients expressing combined polymorphisms are more prone to progression to chronic disease, severe thrombocytopenia and longer disease duration.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12185-023-03551-9.