OBJECTIVE: To establish a method for the simultaneous determination of (R,S)-goitrin, chlorogenic acid, luteoloside and isochlorogenic acid A in Xiaoer ganmao granule. METHODS: HPLC was performed on the column of Hedera C18 with mobile phase of acetonitrile-0.1% formic acid aqueous at a flow rate of 1.0 ml/min, the detection wavelength was 254 nm, 330 nm and 370 nm, column temperature was 40 ℃, and the injection volume was 5 μl, RESULTS: The linear range was 6.6-105 μg/ml for (R,S)-goitrin (r=0.999 9), 9-140 μg/ml for chlorogenic acid (r=0.999 9),9-144 μg/ml for luteoloside (r=0.999 8) and 9-138 μg/ml for isochlorogenic acid A (r=0.999 6); the limits of quantitation were 330 ng, 450 ng, 450 ng and 450 ng, limits of detection were 66 ng, 90 ng, 90 ng and 90 ng, respectively; RSDs of precision, stability and reproducibility tests were lower than 3%; recoveries were 95.01%-98.77%(RSD=1.48%,n=6),95.14%-98.91%(RSD=1.52%,n=6), 95.11%-97.54%(RSD=0.93%,n=6) and 95.58%-99.63%(RSD=1.73%,n=6). CONCLUSIONS: The method is simple and accurate, and suitable for the simultaneous determination of (R,S)-goitrin, chlorogenic acid, luteoloside and isochlorogenic acid A in Xiaoer ganmao granule.