Background: Viral hepatitis was estimated to be the 7th leading cause of mortality globally. About half of this mortality is attributed to hepatitis C virus (HCV). Egypt is the most affected nation by HCV. Human Leucocytic Antigen-G (HLA-G) has an immunosupressor function. Many polymorphisms of HLA-G were reported. Most of those polymorphisms increase HLA-G expression, which increase the susceptibility to HCV infection. Objective: To evaluate the HLA-G 14bp deletion polymorphism on the susceptibility to hepatitis C virus infection. Patients and methods: The study was carried out on 90 subjects (30 females and 60 males) at Al Hussein University Hospital. Their age ranged from 27 to 70 years. They were classified into two groups: Group 1 (control group) included 30 normal healthy subjects (10 females and 20 males), aged 28-68 years and Group 2 (patient group) included 60 patients with HCV infection (20 females and 40 males), aged 27-70 years. All subjects of both groups were tested for detection of HLA-G 14bp deletion polymorphism. Results: The HLA-G 14bp polymorphism was detected in 3 subjects of the control group (10%), while it was detected in 33 patients (54.9%) of the patient group. This revealed a significant increase of HLA-G 14bp deletion (P <0.05) in patient group compared to control group. Conclusion: The HLA-G 14bp deletion polymorphism increased the susceptibility for HCV infection.