Oxidative stress contributes to hepatitis C virus (HCV)-induced liver damage. The activity of antioxidant glutathione S-transferases (GSTs) T1 and M1 is polymorphic. The GSTT1 and GSTM1 genotypes were identified in 139 HCV-infected patients and in 329 healthy individuals. Among patients, there was an excess of GSTT1 (odds ratio [OR], 2.76 [95% confidence interval [CI], 1.77-4.30]; P<.001) and GSTM1 (OR, 1.54 [95% CI, 1.02-2.35]; P=.032) null genotypes and of double-null haplotypes (OR, 3.65 [95% CI, 1.98-6.75]; P<.001). The GSTT1 null genotype, particularly if associated with the GSTM1 null genotype, may facilitate HCV infection becoming chronic.