Background: Hepatitis C virus (HCV) is considered as a main leading cause for cirrhosis and hepatocellular carcinoma (HCC). We aimed to examine the association of IL-6 single nucleotide polymorphisms with the susceptibility of Egyptians to HCV infection. Patients and methods: For comparative purposes, four groups were enrolled; chronic HCV (CHC-group, n=22), HCV-related liver cirrhosis (HCV-LC-group, n= 22), HCV-related HCC (HCV-HCC-group, n=54) and an apparently healthy control group (Control-group, n=48). IL-6 rs-1474347 genotyping was performed using real time PCR assays. Results: For IL-6 rs1474347, AA genotype was more frequent in CHC, HCV-LC and HCV-HCC compared to controls. Conclusion: Screening for IL-6 rs 1474347 AC genotype is considered a good marker for testing the susceptibility of Egyptians to be susceptible for HCV infections and the progression of the disease.