Abstract: OBJECTIVE To investigate clinical characteristics of HCV genotypes of refractory hepatitis C and its effect on antiviral function of Qizhu Granule. METHODS After virus genotypes were analyzed by SANGER sequencing before the treatment， 204 patients with refractory hepatitis C were randomly and equally divided into the treatment group (Qizhu Granules) and the control group (placebo group). Two groups received 48-week treatments. The patients' HCV RNA level was monitored before treatment and during the 4th， 12th， 24th， 48th treatment， as well as 4 weeks after the treatment. RESULTS 182 patients finally received 48-week treatment and completed the study.173 cases were detected with their genotypes， including 129 case of genotype 1b for 74.6%， and 44 cases of non-1b type for 26.4%. No significant difference was found between genotype 1b and non-genotype 1b patients in gender， BMI index and serum ALT and AST level (P>0.05). Patients infected by genotype 1b virus had longer disease courses and were older than non-genotype 1b patients on average. RNA level of HCV of genotype 1b patients was higher than that of non-1b type with significant differences. SVR in the treatment group of non-genotype 1b patients was 42.86%， while that of genotype 1b was only 9.09% with statistically significance. CONCLUSION Non-1b genotype patients have better antiviral effects and HCV genotype is an important factor affecting the antiviral effect of Qizhu granules.