Background: Hemoglobin can develop abnormally as a result of hereditary blood illnesses called ‎thalassemia that are inherited from a person's parents. Objective: The goal of this study was to identify the tumor necrosis factor alpha (TNF-α) A/G polymorphism and correlate ‎TNF-α serum levels with illness progression. Patients and methods: ‎Eighty cases with beta-thalassemia who had been diagnosed at the thalassemia center at ‎Al-Zahra Hospital in Al-Najaf province‎, Iraq participated in a case-control study with 40 ‎healthy individuals serving as the control group. The 80 individuals were divided based on HCV status. From 50 seropositive hepatitis C virus (HCV) patients, 19 had IgG positivity, 15 had ‎IgM positivity, and 16 had both IgG and IgM positivity. All patients and the control group had blood samples taken. DNA from blood was taken ‎to be utilized in PCR to find the TNF-α A/G polymorphism. TNF-α levels were assessed using an ELISA test. Results: The findings explained why HCV-infected individuals had high significant rates of thalassemia ‎than non-infected ones. The findings showed that in thalassemia patients, AA genotype ‎and A allele are risk factors for severity, whereas GG genotype and G allele are ‎protective factors for severity. Conclusions: The findings showed that having an AA genotype increases your chance of contracting ‎HCV. This study also demonstrated a considerably higher level of TNF-α in thalassemia ‎patients compared to controls, as well as a significantly higher level of TNF-α in ‎thalassemia patients who also had HCV infection compared to controls and patients ‎without HCV infection.