A high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI/MS) method for the simultaneous determination of five effective components in Qingrejiedu oral liquid was developed. The HPLC separation was performed on a Zorbax SB C18 column (250 mm x 3.0 mm, 5 microm) using 0.4 mmol/L sodium acetate solution containing 0.2% formic acid (A) and acetonitrile (B) as the mobile phase with gradient elution (0 min, 10% B; 0 --> 6 min, 10% B --> 30% B; 6 --> 15 min, 30% B --> 39% B; 15 --> 16 min, 39% B --> 80% B) at a flow rate of 0.35 mL/min. The analytes were detected by ESI(+)-MS under selected ion monitoring mode (0 --> 9.7 min, m/z 377; 9.7 --> 12 min, m/z 411; 12 --> 14.7 min, m/z 447; 14.7 --> 18 min, m/z 557; 18 --> 25 min, m/z 263). The linear ranges were 0.050-50 mg/L, 0.020-20 mg/L, 0.005-30 mg/L, 0.010-15 mg/L and 0.010-10 mg/L with detection limits of 0.010, 0.005, 0.001, 0.002 and 0.003 mg/L for chlorogenic acid, geniposide, baicalin, forsythin and indirubin, respectively. The average recoveries ranged from 97.0% to 101.7%. The relative standard deviations were less than 2.2%. This method is rapid, accurate, and suitable for the quality control of the five effective components in Qingrejiedu oral liquid.