Objective To investigate epidemic characteristics of HCV and the distribution of naturally occurring resistance mutations of HCVNS5B in Hubei province,and provide the basis for individualized antiviral treatment for HCV infected pa-tients.Methods Collected HCV blood samples of 253 patients from March 2011 to May 2014 in Renming Hospital of Wu-han University,and determined the subtypes of HCVNS5B by first generation of sequencing technology,then compared the result with the nucleotide sequence of HCVNS5B online,located drug resistance loci and record.Results There were 4 gen-otypes and 6 different genetic subtypes in these 253 cases,namely 1a subtype 3,1b subtype 192,2a subtype 38,3a subtype 3, 3b subtypes 11 and 6a subtypes 6.Found 27 gene locus of resistance from 234 different places.The main drug resistance lo-ciare L159F (475-477)26.42%,followed by C316Y (946-948)16.98%,V321I (961-963)15.09% and S282T (844-846) 12.58%.Conclusion The epidemic characteristics of HCV in Hubei province were consistent with those of current in Chi-na;subtype 1b was the main types,followed by 2a subtype.The number of drug-resistant of HCVNS5B was more and com-plex,and presented some popular distributions.It was complex in mutations of 2a subtype,including 13 mutations of natural resistance.There were fewer mutations in subtype 1b,including sites of L159F and C316N.These results may provide the basis for antiviral therapy for HCV patients in this region.