Objective: Numerous studies have unveiled the role of T lymphocytes in the pathogenesis of AA. Specifically, it has been shown that oligoclonally expanded self-reactive T cells induce apoptosis of hematopoietic stem/progenitor cells, this can be mediated either through an interaction via the Fas/Fas-ligand (FasL) pathway or by the production of proinflammatory and growth inhibitory cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) thus resulting in a depletion of the hematopoietic stem cell pool in the BM. TGF-β is a multifunctional peptide, usually produced in latent form and requiring activation to produce a biological response. Also, TGF-β1 has been described as an important negative regulator of haemopoiesis. The aim of this study is to study the association between single nucleotide polymorphisms in TNF- α 308G/A, IFN-γ 874 A/T and TGF-β1 509 C/T genes and susceptibility to aplastic anemia in Egyptian patients. Methods: This study was conducted on 80 participants (40 patients and 40 age and sex matched healthy controls). All patients were diagnosed as acquired aplastic anemia and are under immunosuppressive therapy. We determine SNPs by PCR REFLP technique. Results: As regard IFN-γ 874 there was statistically significant difference between the two groups with more frequent T allele among AA patients than control group (p-value = 0.009) and increased risk of development AA with an odd ratio 3.116 (95% CI 1.184-8.200; P=0.019).There was borderline significant between the two groups with more frequent (GG) among AA patients than control group (p-value = 0.05) and lower risk of development of AA with odd ratio 0.318 (95% CI 0.113-0.893: P=0.026). We found that there were no risk of development of AA with TGF-β1 509 C /T gene polymorphism with odd ratio 0.605 (95% CI 0.250-1.463;P=0.263).Conclusion: Our results confirm the presence of an association between IFN γ gene polymorphism and the risk of development of aplastic anemia.