A novel and rapid method using an ultra-performance liquid chromatography coupled with mass spectrometry was developed and validated for the simultaneous determination of six constituents in ‘Jiang-Zhi’ granule. An acquity UPLC BEH C 18 column (2.1 mm × 50 mm, 1.7 μm) was utilized. Methanol and 0.1% formic acid were adopted in the elution gradient. The selective ion monitor (SIM) mode was used to detect the target compounds. The established method showed a good linearity (R 2 > 0.999 2) over the investigated concentration ranges, good inter-day and intra-day precisions (less than 3%) and good recoveries (from 97.58% to 103.12%) for all six target compounds. The contents of six main components in ‘Jiang-Zhi’ granule could be determined using the established method.