The outcome of antiviral therapy is associated with viral and host factors. In the present study, the association between MHC class I-related chain B () genotypes and therapeutic response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy was investigated in hepatitis C virus (HCV)-infected patients. In total, 107 patients with chronic HCV infection (74 with HCV serotype 1 and 33 with serotype 2) were enrolled. Genotyping of single-nucleotide polymorphism (SNP) rs3828913 and interleukin-28B () SNP rs8099917 was performed using TaqMan SNP genotyping assays. The genotype distribution of the alleles was: CC, 79.4%; CA, 17.8%; and AA, 2.8%. Sustained virological response (SVR) was achieved by 55.1% (59/107) of the HCV patients. The SVR rate of patients with major (CC) alleles was 62.3% and this rate was significantly higher than that of the patients with minor (CA and AA) alleles (27.2%) (P=0.0068). A multivariate logistic model showed that the major genotype was an independent factor contributing to SVR (OR, 4.47; 95% CI, 1.46-13.70; P=0.009). In addition, the genotype was identified as the sole independent factor contributing to SVR and non-virological response in HCV serotype 1 patients with the major genotype. In HCV serotype 2 patients, the genotype was the sole significant factor contributing to SVR (OR, 30.68; 95% CI, 2.72-346.3; P=0.006). In conclusion, the genotype is a strong predictive factor for virological response to PEG-IFN/RBV therapy in HCV patients.