Introduction: 41 Interleukin-18 (IL-18) is a pro-inflammatory cytokine that is induced by hepatitis C virus (HCV) 42 infection. Inter-individual variations of IL-18 gene expression may alter HCV-associated liver 43 injury. Variable single nucleotide polymorphisms (SNPs) have been detected within IL-18 gene 44 sequence. Quantitative assessment of IL-18 plasma level and detection of genotype frequencies 45 of 2 functional polymorphisms of its gene (-607 C/A and -137 G/C) were done to assess their 46 impact on the severity of chronic hepatitis C (CHC). 47 Methodology: 48 Cases group (I) comprised 110 treatment naïve CHC Egyptian patients (78 Males & 32 49 Females, mean age = 40.7±11.8 years) who underwent routine laboratory investigations. 50 Assessment of plasma level of IL-18 was done by enzyme-linked immunosorbent assay 51 (ELISA), detection of IL-18 gene polymorphisms at positions -607 C/A and -137 G/C by 52 polymerase chain reaction sequence specific polymorphism (PCR-SSP) analysis and Liver 53 biopsy with METAVIR scoring were done. The control group (II) comprised 90 healthy 54 participants.