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Objective To analyze the mutations and clinical significance of 10 genotypes associated with genotypes of HBV patients and HBV nucleoside(acid) analogues in Kunming. Methods A total of 2707 patients with chronic hepatitis B who were admitted to the Third People's Hospital of Kunming from May 2017 to March 2019 were enrolled. The Sanger sequencing method was used to treat the common nucleoside(acid) treatment of hepatitis B virus. Gene mutation sites were detected and analyzed for mutation patterns of different resistance. Results Type C accounted for 62.4% of The HBV genotypes in Kunming，fwllowed by 37.3% of type B，and 3.4% of type D. In the 2707 cases ， drug resistance mutations were found in a total of 274 patients(10.1%)，with a mutation rate of 10.12%. Among them， 168 patients developed lamivudine-resistant mutations， and the mutation rate was (6.20%). Drug-resistant mutation sites were mainly concentrated in rtM204V/I and rtL180M， telbivudine (5.68%) and emtricitabine (5.91%) followed by adefovir (1.07%) and entecavir (2.10%). No drug-resistant strains were found in tenofovir，which had the highest sensitivity(99.66%). Conclusion The distribution of HBV genotypes in this region has independent characteristics. As the first-line nucleoside(acid) therapeutic drugs， tenofovir or entecavir， with its highly resistant barrier， has broad application prospects in the treatment of hepatitis B. The use of gene sequencing for the detection of genotypes and drug-resistant mutation sites in patients with chronic hepatitis B is accurate and effective， and can better guide the clinical drug use， providing a powerful objective basis for a precise clinic practice. [ABSTRACT FROM AUTHOR]