Currently available anti-HBV nucleoside (acid) analogues for clinical application include LAM, adefovir, which have been marketed in China, and tenofovir, which has been approved by the US FDA. These drugs are reverse transcriptase inhibitors, which can inhibit HBVDNA replication, but have no direct inhibitory effect on the resting in the nucleus, so it is difficult to completely clear the patient’s body. Coupled with the lack of correction function of HBVDNA polymerase, HBV in patients exists in quasi-species state; with the prolongation of drug use, under the selection pressure of nucleoside (acid) analogs, drug-resistant mutant virus strains gradually become the dominant strains, thus affecting the efficacy. As clinical research on antiviral therapy for chronic hepatitis B (CHB) continues to progress, drug-resistant variants have become the biggest obstacle to the long-term application of nucleoside (acid) analogs, and only by paying sufficient attention to the study of HBV drug resistance can the policy of long-term antiviral therapy be implemented more effectively.