Objective：To explore the virological response，anti-fibrosis efficacy and safety of sofosbuvir and velpatasvir in hepatitis C patients. Methods：Eighty patients with chronic hepatitis C and without cirrhosis were selected as subjects for retrospective analysis. Forty patients in the control group received subcutaneous injection of pegylated interferon α-2b injection and oral ribavirin；forty patients in the observation group one received oral sofosbuvir and velpatasvir；both groups were treated for 12 weeks. Meanwhile，18 patients with compensatory cirrhosis and chronic hepatitis C were selected as the observation group two，which received treatment of sofosbuvir and velpatasvir. HCV-RNA，biochemical indicators，liver transient elastography and adverse reactions before and after medicine treatment were compared. Results：The end of serum virological response rate（95%） and sustained virological response rate（95%） in the observation group were higher than those of 80%（P=0.043） and 72.5%（P=0.006） in the control group. AST and ALT were decreased dramatically after medicine treatment in both groups，especially in the observation group one（P<0.05）. After 12 weeks of treatment，the PCⅢ（125.616±14.683 vs. 25.783±14.006，t=22.091，P=0.000），HA（329.927±66.372 vs. 163.883±55.623，t=8.066，P=0.000） and liver hardness values（19.627±3.594 vs. 15.300±3.645，t=3.456，P=0.003） of patients complicated with compensated cirrhosis in the observation group two were significantly lower. The incidence of adverse reactions in the control group（52.5%） was nearly twice than that in the observation group one（25%）（P<0.05）. Conclusion：Compared with combination of pegylated interferon α-2b combined and ribavirin，combination of sofosbuvir and velpatasvir has better curative effect，lower adverse effect and higher safety and can also delay the progression to liver fibrosis.