Objective: To apply ultra performance liquid chromatography (UPLC) to establish a method for the simultaneous determination of taxfolin and quercetin in Polygoni Orientalis Fructus. Methods: The separation was performed on an Agilent ZORBAX SB-C18 column with the gradient elution of acetonitrile-0.1% phosphoric acid in water as the mobile phase, the column temperature was 25℃, the detection wavelength was 290 nm, the flow rate was 0.2 mL·min-1, and the injection volume was 1 μL. Results: The established analytical method was well investigated methodologically. The linear ranges were 3.258~104.272 μg·mL-1 and 2.983~95.452 μg·mL-1 for taxfolin and quercetin, respectively, and the average recoveries were 98.8% with RSD values of 1.9% and 2.2%. Conclusion: The method is simple, rapid, and can determine the contents of taxfolin and quercetin at the same wavelength, which can provide a reference basis for the quality control of Polygoni Orientalis Fructus.