OBJECTIVE： To evaluate therapeutic efficacy of lamivudine （LAM） combined with adefovir dipivoxil （ADV） in the treatment of LAM-resistant chronic hepatitis B patients， and to study the relationship of therapeutic efficacy with hepatitis B virus （HBV） genotype. METHODS： A total of 101 LAM-resistant chronic hepatitis B patients selected during Dec. 2012 to Dec. 2014 were given LAM+ADV for 24 months at least. Regular outpatient visits or telephone follow-up were also performed. Polymerase chain reaction-reverse dot blot method was used to determine the HBV genotype. Chi-square test， Kaplan-Meier method and Log-rank test were used to compare the virological response （HBV-DNA clearance rate） and biological response （ALT normalization rate and HBeAg seroconversion rate） among different genotypes at the 6th， 12th， 18th and 24th month of follow-up. RESULTS： The follow-up rate was 100％， without missed follow-up. Two genotypes were detected， including 34 patients （33.7％） with genotype B and 67 patients （66.3％） with genotype C. At each time point mentioned above， the HBV-DNA clearance rates of 101 patients were 34.7％， 55.4％， 79.2％ and 93.1％. At 6th month， HBV-DNA clearance rate and accumulative HBV-DNA clearance rate of genotype B were significantly higher than genotype C， with statistical significance （P＜0.05）. There was no statistical significance in HBV-DNA clearance rates or accumulative HBV-DNA clearance rates between different genotypes at other time points （P＞0.05）. At each time point mentioned above， ALT normalization rates of 101 patients were 40.6％， 69.3％， 82.2％， 84.2％； there was no statistical significance in ALT normalization rates or accumulative ALT normalization rates between different genotypes （P＞0.05）. At each time point mentioned above， the HBeAg seroconversion rates of 101 patients were 10.9％， 19.8％， 24.8％， 29.7％； there was no statistical significance in the HBeAg seroconversion rates or accumulative HBeAg seroconversion rates between different genotypes （P＞0.05）. CONCLUSIONS： LAM combined with ADV is effective for LAM-resistant chronic hepatitis B patients. Moreover， the combination therapy can achieve earlier viological response in patients with genotype B than those with genotype C.