Objectives: We aimed to find the relation between the gene polymorphisms in interleukin-10 and interferon- γ genes with susceptibility and severity of HCV infection among Egyptian patients. Patients and methods: Interleukin-10 -592 A/C, -1082 G/A and IFN-γ +874 T/A genotypes were determined in 50 chronic HCV patients, 50 HCV cirrhotic patients and 50 health controls. Results: IL10-592A/C polymorphism genotyping revealed that the frequency of CC genotype was significantly higher in chronic HCV patients than in controls (58% versus 30%, p < 0.05). Regarding IL10-1082 G/A polymorphism genotyping, a higher frequency of GG genotype was found in chronic HCV patients compared to controls (31% versus 10%, p < 0.05). IFN-γ -874 T/A genotyping showed that TT genotype was significantly higher in chronic HCV participants than controls (31% versus 18%, p < 0.05) while a higher frequency of T allele was found in cirrhotic patients compared to non- cirrhotic (p < 0.05). Conclusion: Our observations suggested that IL10-592A/C,-1082G/A, and IFN-γ -874 T/A polymorphisms had strong association with susceptibility to HCV infection, also the frequency of IFN-γ -874 T allele was higher in cirrhotic patients.