Objective To investigate the relationship between hepatitis B virus genotype and lamivudine-resistant YMDD mutations and the clinical significance.Methods A total of 150 cases with chronic hepatitis B (CHB) were chosen from the outpatients and inpatients in our hospital.By testing the serum before and after they have taken lamivudine for 12 months,hepatitis B virus (HBV) genotype,HBV DNA quantitation,and YMDD mutation were tested applying polymerase chain reaction (PCR)-reverse dotblot (RDB) hybridization and real-time quantitative PCR.Results Of the 150 patients,81 (54.00％) were HBV subtype B;67 cases (44.67％) were HBV subtype C,and 2 cases (1.33％) were mixtures of HBV B and D.Before taking lamivudine,6 patients were found to have YMDD mutation in their serum,the genotype was HBV subtypes B.After taking lamivudine for 12 months,YMDD mutation was detected in 32 cases,of whom the proportion of HBV subtypes B was 24.69％ (20/81);the proportion of HBV subtype C was 17.91％;the difference was statistically significant (P ＜ 0.05).Conclusion The prevalence of YMDD mutation was associated with hepatitis B virus genotype.