Shugan Quzhi capsule is a hospital preparation of Xinhua Hospital affiliated to School of Medicine, Shanghai Jiaotong University. It has been used for the treatment of adult patients with fatty liver caused by obesity, high cholesterol and other factors. In the present study, we established an ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to simultaneously determine 4 saponiningredients including Notoginsenoside R1, Ginsenoside Rb1, Ginsenoside Re and Ginsenoside Rg1 present in Shugan Quzhi capsule. The chromatographic separation was conducted on ZORBAX SB-C18 (2.1 mm×50 mm, 1.8 μm). The mobile phase was composed of acetonitrile and aqueous solution consisted of 0.05% formic acid and 5 mM ammonium acetate. Gradient elution rate was 0.3 mL/min, the column temperature was 40 ºC; MS was conducted using electrospray ionisation (ESI) and multiple reaction monitoring (MRM) coupled with positive and negative scanning switch. With which, Ginsenoside Re and Ginsenoside Rg1 were detected using negative ion mode detection while Notoginsenoside R1, Ginsenoside Rb1 and internal standard (Ginsenoside F1) were detected using positive ion mode detection. The limits of quantification (LOQ) for Notoginsenoside R1, Ginsenoside Rb1, Ginsenoside Re and Ginsenoside Rg1 were 6.54×10–4, 2.57×10–4, 0.11 and 6.91×10–3 ng/mL, respectively. The limits of detection (LOD) for these compounds were 1.96×10–4, 7.70×10–5, 3.45×10–2, and 2.07×10–3 ng/mL, respectively. All calibration curves showed a good linearity (r2>0.9633) within the test range. The intra- and inter-day precisions (relative standard deviation, RSD) were lower than 5% and the average recoveries were in the range of 80%–120%. With this method, four kinds of saponins were separated and detected in 6 min. This method is simple, rapid and shows high sensitivity and accuracy.