Background and study aim : Chronic Hepatitis C virus (HCV) infection is typically characterized by slowly progressive hepatic fibrosis. However, it is recognized that some patients do not progress while others rapidly develop significant fibrosis. Immune response mechanism in the control of viral replication and persistence in HCV induced liver disease has been well documented. Solute carrier 11a1 (SLC11A1) plays an immunomodulatory role in influencing macrophage activation status and the T helper 1/T helper 2 biases. It modulates the susceptibility to infectious/autoimmune diseases. The study aimed to: Analyze the possible involvement of polymorphism in the promoter regions of the SLC11A1 gene in the susceptibility for chronic hepatitis C infection and the progression of fibrosis in these patients. Patients and methods: This study included 138 subjects. They were classified into 2 groups: Group I that included 69 matched apparently healthy persons and Group II that included 69 chronic hepatitis C patients (Child A) and was divided into 2 subgroups: Group (IIA): It included 35 chronic hepatitis C patients without fibrosis and Group (IIB): It included 34 chronic hepatitis C patients with fibrosis. All individuals were subjected to: Full history taking, complete physical and clinical examination, abdominal ultrasound, fibroscan, routine laboratory investigations, viral markers and determination of SLC11A1 promoter gene polymorphism. Results: The present study demonstrated that no statistically significant difference was observed in the distribution of SLC11A1 genotype frequencies among patient and control groups, suggested absence of association between the presence of the polymorphism and the prevalence of disease. Moreover, chronic hepatitis C patients who had SLC11A1 2/2 genotype were significantly at decreased risk to develop fibrosis 0.2 times than those who had 3/3 genotype [OR:0.2, CI:(0.52-0.79)] suggesting that the 2/2 genotype is associated with an decreased susceptibility to develop fibrosis. Conclusion and recommendations: SLC11A1 gene promoter polymorphism could influence fibrosis progression in chronic hepatitis C in that the homozygous genotype 2/2 exerts a protective effect against cirrhosis development. Gene therapy may have an important role in the treatment and prognosis of HCV infection which need further studies.