A cell extraction coupled with high-performance liquid chromatography (HPLC) analysis has been developed to screen the potential bioactive components in combined prescription of Danggui Buxue decoction. The method was validated by using HL-7702 cells, RAW 264.7 cells and Caco-2 cell extraction. According to the hypothesis that, when cells are incubated together with the extract of traditional Chinese medicines (TCMs), the potential bioactive compounds in the extract should selectively combine with the cells, cell-combining compounds were analyzed by HPLC-diode array-evaporative light scattering detectors. Their structures were elucidated in comparison with available reference compounds, and further confirmed by HPLC-electrospray ionization time-of-flight mass spectrometry with accurate mass measurement. The results demonstrated that nine compounds were combined with the HL-7702 cells, seven with RAW 264.7 cells, and thirteen with the Caco-2 cell line. In view of the two key steps of drugs action, absorption by intestinal epithelium cells and interaction with target cells, this rapid and reliable method could be utilized to predict the bioactive constituents in TCMs, and it was in agreement with the characteristics of combined prescriptions of TCMs as multi-components, multi-target sites and multi-channel actions.