This study was designed to clarify the chemical constituents in Yuanhu Zhitong prescription (YHZT), a rapid high performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (HPLC-QTOF/MS) method was established. Based on the high resolution MS spectra data, fragment ion information, reference standards data and literature reports, 51 peaks including 28 alkaloid compounds and 23 coumarin compounds were identified. The chemical constituents in YHZT were rapidly, accurately, systematically analyzed. The results lay a foundation for the quality control of effective compounds of YHZT.