Abstract: DNA fragmentation in peripheral blood lymphocytes is a reliable marker for oxidative stress occurring in the liver of chronic hepatitis C (CHC) patients which reflects a direct genotoxic effect of the virus and suggests a same genotoxic effect that might operate in the liver. Previous studies have investigated DNA damage in peripheral leukocytes of CHC patients, but none focused on genotype 4. This work aimed at examining DNA damage in different treatment outcomes of genotype 4 infection. The study included 80 viral hepatitis C genotype 4 patients and 80 healthy volunteers. HCV-RNA was detected by real-time PCR, genotype was defined by INNO-LiPA and DNA damage was assayed using alkaline Comet assay. The mean percentage of DNA damage was significantly higher in patients' group than in control group (p<0.01) and in null response (48.75±11.12) and breakthrough response (49.33±1.03) patients than in SVR patients (22.78±13.95) (p<0.05/3). Comet results revealed that all breakthrough and null response patients have DNA damage. Interestingly, 78.5% of SVR patients had DNA damage (64.3% showed mild damage and 14.2% showed marked damage). In conclusion, in genotype 4; despite clearance of serum HCV-RNA and apparent clinical resolution; SVR patients might not experience infection clearance and should be followed up being at suspected risk for virus reactivation.