Background: Chronic HCV Patients taking PEG-IFN-alpha/R from different ethnic groups have different probabilities of reaching a sustained viral response (SVR). There are many influence factors, such as HCV genotype, IL-28B single-nucleotide polymorphisms (SNP), Fibrosis 4 index (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) score. But the baseline factors in relation to treatment outcome was still not much clear. Methods: We evaluated data from 231 chronic HCV patients with or without liver fibrosis and their antiviral efficacy after treatment with pegylated interferon plus ribavirin (PEG-IFN-alpha/R) for 24-48 weeks. IL-28B SNP and HCV genotypes were analyzed with genome sequencing using pyrosequencing. Results: Sustained viral response (SVR) rates of patients with HCV 1b and 2a genotypes were 52.25% (58/111) and 75.28% (67/89) (P3.25. In addition, when their APRI >2, only 30.3% of HCV 1b patients and 50.2% of HCV 2a patients could obtain SVR. Conclusions: There were high proportion of HCV genotype 1b and 2a in Northwest China. In both HCV 1b and 2a genotypes, patients with protective-genotype of IL-28B were more likely to obtain SVR. However, those with significant fibrosis or cirrhosis were less likely, no matter their genotype. Combined factors of HCV genotype, IL-28B genotype, FIB-4 and ARPI may indicate high prediction and clinical value regarding treatment with PEG-IFN-alpha/R and prognostic evaluation of chronic hepatitis C patients.