Abstract : Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. The long-term natural history of HCV infection is highly variable. Hepatic injury can range from minimal histological changes to extensive fibrosis and cirrhosis with or without hepatocellular carcinoma. There are approximately seventy-one million chronically infected individuals worldwide. The aim of this study is to analysis of the contribution of genetic (single nucleotide polymorphism (SNP) at position 3116996 of HLA on increase risk of progression of liver fibrosis in Chronic Hepatitis C Egyptian Patients. Eighty-five cases included in our study divided into three groups: Group 1; included twenty cirrhotic patients with HCV, group 2; included twenty non-cirrhotic patients with HCV, group 3 included forty-five control normal persons having no HCV with age group range from (18-60). All patients had negative serology for HIV and HBV with normal BM1 and no metabolic liver disease or alcohol consumption. HLA-DPB1 (SNPrs3116996) genotype and their alleles frequencies were found to be statistically different between HCV groups and control. HLADPB1 SNPrs3116996 polymorphisms increase the risk of cirrhosis. In HCV patients, HLA-DPB1 gene rs3116996 AG genotype increase risk of Cirrhosis risk. HLA DPB rs3116996 TA affects liver fibrosis severity.