OBJECTIVE: To establish a method for the simultaneous determination of narirutin, naringin, hesperiden and neohesperiden in Weisu granule. METHODS: UPLC was performed on the column of ACQUITY UPLC BEH C18 with mobile phase of acetonitrile-0.2% Phosphoric acid aqueous(gradient elution) at a flow rate of 0.40 ml/min, the detection wavelength was 284 nm, the column temperature was 30 ℃, and the injection volume was 1 μl. RESULTS: The linear range was 9.38-93.75 μg/ml for narirutin(r=0.999 7), 32.25-322.50 μg/ml for naringin(r=0.999 7), 11.25-112.50 μg/ml for hesperiden(r=0.999 9) and 11.88-118.75 μg/ml for neohesperidin(r=0.999 8);limits of quantitation were 20 ng, 18 ng,18 ng and 18 ng,the limits of detection were 6 ng,5 ng ,5 ng and 5 ng, respectively; RSDs of precision, stability and reproducibility tests were lower than 2.0%; recoveries were 96.24%-103.12% (RSD=2.45%,n=6), 98.43%-102.10% (RSD=1.42%,n=6), 96.10%-101.41% (RSD=2.07%,n=6) and 95.57%-99.06% (RSD=1.44%,n=6), respectively. CONCLUSIONS: The method is rapid and efficient, and suitable for the simultaneous determination of narirutin, naringin, hesperiden and neohesperiden in Weisu granule.