Abstract: Objective To analyze the genotypes, drug resistant distribution and drug mutation sites of hepatitis B virus(HBV) in chronic hepatitis B(CHB) patients in Huaibei, Anhui province.Methods A total of 141 CHB patients with HBV-DNA positive who were admitted to Huaibei General Miners Hospital and their branch hospitals from January 2018 to December 2020 were selected and their serum samples were collected. Their HBV-DNA was quantified by fluorescence quantitative PCR. Their HBV genotypes were determined by PCR-RFLP method. The drug-resistant sites in the P region of HBV gene were analyzed by Sanger sequencing.Results Among the 141 CHB patients, 109 patients were successfully classified, where genotype C accounted for the most(71.56%), followed by genotype B(17.43%), and genotype B+C was the lowest(11.01%). The drug-resistance mutation rate of these CHB patients was 25.69%, where type C(28.21%) was the highest. The drug resistance rate of nucleoside analogs was highest in lamivudine and adefovir(60.71%), followed by telbivudine(25.00%), and entecavir was the lowest(3.57%). About 16 drug resistance mutation types and 3 mutation patterns were detected in the P region, most of which were type C. Among them, adefovir was mainly rtN236T and rtA181T/S; lamivudine was mainly rtL180M+M204I/V, followed by rtA181T and V207M; entecavir was mainly rtA181S+T184N; telbivudine was mostly rtL180M+M204I/V.Conclusions The genotype of CHB patients in Huaibei is mainly genotype C. The drug-resistant mutation rate of genotype C is higher than that of genotypes B and B+C. The resistant type of nucleoside analogs are mainly genotype C, and the mutation pattern is relatively complex. Patients with different HBV genotypes have different drug-resistance mutation sites, so it is necessary to detect HBV genotypes and related drug-resistance mutations in CHB patients during treatment with nucleoside analogs, so as to improve the efficacy of antiviral therapy.