Background: Tumor necrosis-alpha (TNF-α) is produced by macrophages, neutrophils, T-cells and NK-cells after stimulation. In turn, TNF-α can stimulate secretion, increase the expression of adhesion molecules as well as active neutrophils. Hence, it fulfills the role as a principal mediator of cellular immune response and inflammation, and may play an important role in non-cytopathic and cytolytic clearance of hepatitis B virus (HBV). The clearance of HBV is a complex process which may be influenced by many factors including polymorphisms in the tumor necrosis (TNF-) gene promoter. Aim of the work: The study aimed to determine the TNF-α as a gene expressed in chronic hepatitis B virus infection and its role in outcome of the virus. Patients and methods:  Ninety four patients with chronic  HBV infection, their age between 19 and 59 years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during treatment and twenty healthy individuals were included to serve as controls. All the patients and controls were subjected to the following; history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, and serological assay for HBsAg, HBsAb, HBeAg, HBeAb, HBV DNA (quantitative), and TNF-α promoter polymorphisms in two sites 238 and 308. Results: The prevalence of the variant at position -308 GA was similar in all investigated groups (patients and controls).An association was found between the TNF-α promoter polymorphism at position -238 and the development of chronic HBV infection with sensitivity of 93% and specificity of 75%. Conclusion: TNF-α-308 GA was significantly associated with clearance, showing protective antibody and persistent HBV infection. The promoter variant of TNF-α at position 238 GA, GG appears to be linked to defective viral clearance, controls had higher TNF-α-238 GG,GA, AA as compared to cases with significant difference. Recommendations: The variation in the genes governing the levels of constitutive and inducible TNF-α might be an important factor, which might explain the variable outcome of HBV infection.