〔Abstract〕 Objective To analyze the cause of drug resistance of hepatitis B virus by studying mutation sites the of HBV RT region under nucleoside(acid) analogues in Jiangxi Province. Methods Serum samples of 104 outpatients receiving NAs antiviral therapy for more than one year were collected, and fragments of possible drug-resistant mutation sites in HBV RT region were amplified. The levels of HBV DNA and ALT with poor response and salvage treatment for 1 month were collected to analyze the effect of salvage treatment. Nucleic acid and amino acid sequences were compared by BioEdit software package to analyze the main variant types in RT region of patients and their distribution with different genotypes. DataMonkey online software was used to analyze the selection pressure and positive selection sites of different genotypes. Results After salvage treatment, HBV DNA and ALT levels decreased, and HBV DNA levels decreased more significantly, but there was no difference among different genotypes. Of 104 patients, 87 were associated with drug resistancE-related mutations, 14(13.46%) were multi-site resistance mutations(3 or more sites); 7 of the remaining 17 patients did not detect the drug resistance mutation,10 were possible drug resistance mutation sites. M204 I + L180 M site mutation rate in genotype C was higher than that of genotype B,and the difference was statistically significant. Analysis of selection pressure showed that there was no difference in selection pressure between the two genotypes,and neutral selection was the main choice. Rt207 and rt229 were positive selection sites in genotype B,but not in genotype C. Conclusion Genotypes B and C are most common types in chronic hepatitis B patients in Jiangxi Province,and the M204 I locus variation is dominant.Positive selection sites are detected in Genotype B,so the widespread use of nucleoside analogues promote the emergence of new gene functions,and may also be the cause of multiple new drug resistance sites.