Background: hepatitis C virus (HCV) is responsible for nearly 80 - 90% of post-transfusion hepatitis in beta-thalassemia patients. This study aimed to evaluate the appearance of HCV infection in a set of Beta-Thalassemia patients in Baghdad and to assess the IL-12, IL-18, and serum liver enzymes levels among β-thalassemic patients infected with HCV. Methodology: A total of 150 sample included in this study, (70 male; 70 female) in Baghdad, 140 beta-thalassemia patients, and 10 healthy control group, from January to September, 2020. Sera of study populations were tested for anti-HCV Ab by ELISA and confirmed by western blot technique;the concentrations of IL-12, IL-18, AST, ALT, and APL were also measured. Results: 17.9% (n=25/140) of the major thalassemic patients were positive for HCV Abs.The median of serum concentrations for IL-12 in HCV positive thalassemic patients was 0.41 pg/ml which is lower than the corresponding medians of control group while the median concentration of IL-18 in sera of HCV positive thalassemic patients was 17.07 pg/ml, which is significantly higher (p < 0.001) than the corresponding median in control group. The median concentration of AST in sera of HCV positive thalassemic patients was 71.0 U/L which was significantly higher than the equivalent medians in HCV negative thalassemic group and control group while. The correlation coefficient for anti-HCV Abs concentrations and their corresponding IL-12 concentrations is 0.084; while for the same antibodies with IL-18 was 0.0979. Conclusion: The prevalence of HCV infections is high among β-thalassemia major patients in Baghdad, especially among young adult patients. ELISA technique is a perfect choice for detecting anti-HCV Abs with very high sensitivity. Generally, the infected patients have decreased IL-12 concentrations, elevated IL-18 concentrations, and elevated serum AST concentrations.