Abstract: QingGanSanJie decoction (QGSJ), which consists of 14 different herbs, is a multiherbal formula for liver cancer that is administered in different combinations based on experimental observations and clinical experiences from long-term applications. A method based on accelerated solvent extraction (ASE) followed by high-performance liquid chromatography (HPLC) coupled with electrospray time-of-flight mass spectrometry (ESI-TOF MS) were established for simultaneous determination of 29 chemical components in QGSJ. The operational parameters of ASE, including the extraction solvent (70% ethanol), extraction temperature (100 ℃), static extraction time (5 min), and extraction cycles (two cycles) were optimized by orthogonal design and principal component analysis. HPLC separation was performed on a Kromasil C18 HPLC column with a linear gradient mobile phase system. TOF MS was set in negative ion mode with a detector range of m/z100-1100. The results show that 29 compounds in the QGSJ have good linearity (r>0.994), and intra-day and inter-day precision (relative standard deviation) are less than 5%. The extraction recoveries of the 29 compounds range from 96.5% to 104.5%. The method is rapid and reliable, which is suitable for the quantitative evaluation of multiherbal traditional Chinese medicine.