Objective To build a method to simultaneously determine paeoniflorin, naringin, hesperidin, glycyrrhizic acid in Sinisan by HPLC, provide a reliable method for evaluation and effective quality control, and lay the foundation of material basis for efficacy research for TCM compound Sinisan.Methods The column was Kromasil C18 (4.6 mm×250 mm, 5μm);mobile phase was acetonitrile-0.05% phosphoric acid aqueous solution with gradient elution program;the flow rate was 1.0 mL/min;UV detection was performed at 240 nm;the detector drift tube temperature was set at 30℃.Results The linear ranges of paeoniflorin, naringin, hesperidin and glycyrrhizic acid were 0.00225-0.01125μg (r=0.999 7), 0.00390-0.00195μg (r=0.9997), 0.00198-0.00099μg (r=0.999 5), 0.00262-0.00131μg (r=0.999 7), respectively. The average recoveries of paeoniflorin, hesperidin, naringin and glycyrrhizic acid were 97.72% (RSD=1.02%), 98.45% (RSD=1.52%), 97.74% (RSD=1.63%), 98.34% (RSD=1.78%), respectively.Conclusion The method is accurate, simple, reliable and duplicable, and is available for the quality control of Sinisan.