Background and Aim: Infection with hepatitis C virus (HCV) is the major cause of chronic liver disease worldwide, but few of patients are able to clear the virus naturally. Interleukin-10 (IL-10) is a multifunctional cytokine with anti-inflammatory properties that can suppress the immune response against HCV. Interindividual  Variations in IL-10 production are genetically contributed by polymorphisms within the IL-10 promoter region. This study aimed to investigate the association of the IL-10 gene promoter (−1082 G/A) polymorphism with HCV infection susceptibility in Egyptian individuals ,also study relation between different genotypes in this promoter region and liver histopathology, in addition to studying correlation between different biochemical parameters including ALT,AST,TNF-alpha, Albumin, Total serum bilirubin, Platelets count.  Methodology: Two hundred chronically infected patients and one hundred controls were enrolled in the study. IL-10 (−1,082 G/A) genotyping was performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR).TNF-alpha serum level was assessed by ELISA, other biochemical analysis were performed using aRoche Hitachi chemistry analyzer(USA).METAVIR scoring system was used to assess necroinflamation and fibrosis in liver biopsy.  Results: Under the dominant model for IL-10 (-1082G/A), (AA vs.GA;GG) we found a higher frequencies of A allele and GA genotype in patients group (A 53.5% : GA 45%) on the other hand; A positive correlation was found between IL-10 gene polymorphism and liver fibrosis ,also appositive correlation between ALT & AST, ALT & T.S. Billirubin, ALT & TNF-α, AST & T.S. Billirubin, AST & TNF-alpha, Billirubin& TNF- α with (P<0.001), A highly negative significant correlation between ALT & PLT, AST & PLT, TNF-alpha &Platelets (P<0.001)  Conclusions: Our findings suggest a possible association between IL-10(-1082 G/A) promoter polymorphism and HCV infection, which may confer a higher risk for developing HCV infection.