A method for the determination of main degradation products including mono-POM PMEA, adefovir and other impurities in adefovir dipivoxil was established.The Welch Materials XB-C8 column (250 mm × 4.6 mm, 5 μm) was adopted with the mobile phase consisting of buffer solution-acetonitrile (65:35), the buffer solution contained 50 mmol · L-1 potassium phosphate dibasic and 10 mmol · L-1 tetrabutylammonium hydrogen sulfate, and was adjusted to pH 3.0 with phosphate acid.The detection wavelength was 260 nm, and the flow rate was 1.0 mL · min-1.The baseline separation was achieved between the main peak of adefovir dipivoxil and the near peak of impurities, and the resolutions among the main degradation products (i.e., adefovir, mono-POM PMEA and 9-[2-(diethyl-phosphonomethoxy)ethyl]adenine) were above 2.0.The good linearity was obtained over the range of 0.109-21.8 μg · mL-1 for adefovir, 0.111-22.2 μg · mL-1 for mono-POM PMEA, and 0.105-21.0 μg · mL-1 for adefovir dipivoxil.The average recoveries were 98.8% for adefovir and 99.7% for mono-POM PMEA, resp.This method is simple, accurate, with well specificity, and can be applied to determination of the relative substances in adefovir dipivoxil and quality control.