Background: Intra-familial transmission of hepatitis C virus (HCV) in Egypt was found to play a major role in the high prevalence of HCV in Egypt. A single nucleotide polymorphism (SNP) near the interleukin-28B (IL28B) (rs12979860) gene is associated with self-cure of Hepatitis C Virus (HCV). Aim of the work: To determine the significance of IL-28B (rs12979860) gene polymorphism in intra-familial transmission of HCV in Egypt, Patients and Methods: Three hundred HCV patients, 860 family members and 100 healthy subjects were studied. HCV antibodies test was done by Enzyme Linked Immunosorbent Assay (ELISA) for all family members. Real-Time Polymerase chain reaction (PCR) ascertained presence of chronic HCV. PCR and restriction enzyme analysis were used to determine the molecular structure of IL-28B (rs12979860) gene to all studied subjects. Results: The distribution of IL-28B (rs12979860) gene polymorphism in patients was 24.3%, 53.7% and 22% for C/C, C/T and T/T genotypes respectively, in infected family members was 27.5%, 54.9% and 17.6% for C/C, C/T and T/T respectively and in negative family members was 28.5%, 54.1% and 17.4% for C/C, C/T and T/T respectively. C/C genotype was significantly more frequent in non-infected family members while T/T genotype was significantly more frequent in HCV infected patients when compared with controls. Conclusions: Our study concluded that IL-28B (rs12979860) gene polymorphism has no impact on intra-familial transmission of HCV.