Abstract: Objective　To analyze comparatively and find a sensitive detection method for hepatitis B virus（HBV） YMDD mutation. Methods　A total of 166 samples from patients with HBV infection were collected，including 116 cases treated by lamivudine for 1 year and 50 cases treated by telbivudine for 1 year. The comparison of 3 HBV YMDD mutation detection methods real-time polymerase chain reaction（PCR），high temperature ligase detection reaction（LDR） and sequencing was analyzed. In addition，the sensitivities of the 3 methods were detected. Results　The positive rates of LDR，real-time PCR and sequencing were 23.49%，21.68% and 19.27%. The specificities of the 3 methods were 100%. In the cases treated by lamivudine，there were 38 cases with mutation（12 YIDD and 26 YVDD）. There was only 1 case with YIDD mutation in the cases treated by telbivudine. Conclusions　The LDR for detecting YMDD mutation is suitable in clinical application，and YVDD mutation is more common than YIDD mutation.

Key words: Hepatitis B virus, Mutation, High temperature ligase detection reaction, Sequencing