HPLC was used to determine the dissolution of lamivudine tablet. The lamivudine tablet was dissolved in water 900 mL at 50 r/min, and test sample was obtained at 30th min for HPLC determination Sunfire C18 (150 mm × 4.6 mm, 5 μm) column was used with acetate buffer (pH = 3.8 ± 0.2)-methanol (95:5) as mobile phase at a flow rate of 1.0 mL/min. The detection wavelength was 277 nm. External standard method was used to determine dissolution of lamivudine tablet. The linear range of lamivudine was 0.015-0.3 g/L (r = 09999). Average recoveries were 99.7%, and RSD was 0.99% (n = 6). The dissolution of lamivudine tablet was qualified. The method is simple, easy, with accurate result.