Abstract: OBJECTIVE To establish and optimize the determination method of multi index content in Daqili San, so as to improve its quality standard. METHODS HPLC multi wavelength switching method was established to determine the content of naringin, ginsenoside Rg1, draconotin perchlorate, emodin and chrysophanol in Daqili San. By using the central composite design-response surface(CCD-RSM), the extraction process of content determination was optimized, and the verification and methodology evaluation were carried out. RESULTS The best processing conditions of multi index content in Daqili San were as follows:solvent content was 40 mL; methanol concentration was 75%; ultrasound time was 25 min. The average content of naringin, ginsenoside Rg1, draconemin perchlorate, emodin and chrysophanol were 0.74, 2.80, 1.33, 0.26, 0.29 mg·g^-1, respectively. The calibration curves were linear, the average recoveries ranged from 96.75% to 100.01%, RSD ranged from 0.98% to 1.94%. CONCLUSION By using CCD-RSM to optimize extraction process of multi index content determination in Daqili San, the actual and predicted values are highly consistent with good predictability, and the method is feasible. The multi index content determination method established by HPLC multi wavelength switching method is stable, accurate and reliable.