Objective To investigate the incidence of natural resistance mutations to direct- acting antiviral agents( DAAs) in patients with chronic hepatitis C( CHC) in Beijing,China,and to compare the natural resistance mutations to DAAs in interferon( IFN) / ribavirin( RBV) treatment- experienced and treatment- nave patients. Methods A total of 101 CHC patients with genotype 1b who visited Peking University First Hospital from July 2009 to November 2013 were enrolled,among whom 40 patients were once treated with IFN / RBV and 61 patients were not treated with IFN / RBV. The patients' HCV RNA was extracted,and polymerase chain reaction was applied for amplification. The genes in HCV NS3,NS5 A,and NS5 B regions were sequenced,sequence alignment and resistance analysis were performed,and the incidence of natural resistance was compared. The t- test was applied for comparison of normally distributed continuous data between groups,and the Mann- Whitney U rank sum test was applied for comparison of abnormally distributed continuous data between groups. The chi- square test or Fisher 's exact test was applied for comparison of categorical data between groups. Results The sequences of NS3,NS5 A,and NS5 B regions were obtained from 84( 83. 17%),92( 91. 09%),and 97( 96. 04%) patients,respectively. The natural resistance mutations to DAAs in NS3 region occurred in 7 patients( 8. 33%)( T54 S,n = 1,1. 19%; R117 H,n = 5,5. 95%; N174 F,n = 1,1. 19%),those in NS5 A region occurred in 19 patients( 20. 65%)( L28 M,n = 7,7. 61%; L31 M,n = 1,1. 09%; P58 S,n = 4,4. 35%; Y93 H,n = 7,7. 61%),and those in NS5 B region occurred in 95 patients( 97. 94%)( L159 F,n = 1,1. 03%; C316 N,n = 92,94. 85%; A421 V,n = 6,6. 18%; R422 K,n = 1,1. 03%; M426 L,n = 3,3. 09%; V499 A,n = 38,39. 18%). The incidence of resistance mutations to DAAs in NS3,NS5 A,and NS5 B regions showed no significant difference between the IFN / RBV treatment- experienced and treatment- nave patients( all P > 0. 05). Conclusion Natural resistance mutations to DAAs exist in the treatment- nave CHC patients with genotype 1b in Beijing. Most of these mutations are low resistance mutations,and their effects on the clinical efficacy of DAAs need further investigation. The association between IFN / RBV treatment and increased natural resistance mutations to DAAs was not observed in CHC patients.