Objective: Two interleukin (IL-18) Polymorphisms ( - 607 C/A and -137 G/C ) and their haplotypes are known to affect the IL-18 expression. A number of SNPs ( single nucleotide polymorphisms ) that influence IL- 18 production are found in the gene promoter region.   Aim of the work: The study will determine HCV clearance or persistence as a result of IL-18 promoter polymorphisms (-607 C/A and 137 G/C ) in chronic hepatitis C virus infected patients during interferon and ribavirin treatment.   Patients and methods: Eighty patients with chronic hepatitis C virus infection, their age  ranges between (23-57) years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during interferon and ribavirin therapy and fifteen healthy individuals were included to serve as controls. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, CBCs and serological assay and specific sequence primer polymerase chain reaction (PCR) IL-18-137, 607 SNP.   Results: There was no significant difference in the frequencies of -137 allelic distribution in CHCV infection patients and healthy controls. The -607 AA allele was higher among controls than in patients with CHCV infection. The -607 CC allele was higher among the CHCV patients than in the healthy controls.  87.5 % of the studied CHCV patients had response to IFN therapy, the majority of cases had A1F1 biopsy results.   Conclusion: IL-18 promoter polymorphism at -607 position with AA allele is a potential protective marker, as it is higher among healthy controls than the CHCV patients.   Recommendations: that IL-18 could be considered as a target for therapeutics.