Affinity ultrafiltration coupled with liquid chromatography-mass spectrometry (LC-MS) technology is a rapid, simple and effective method for discovering active components, which is especially applicable to the complex extracts of traditional Chinese medicines (TCMs). Affinity ultrafiltration can facilitate the rapid separation of small-molecule ligands from the target macromolecules, and LC-MS contributes to the structural identification of potential active compounds. Combination of the two techniques is vital to reveal the effective materials of TCMs and helpful for the TCM-based drug discovery. In this review, according to the studies in recent years, we make a brief introduction about the application of the ultrafiltration coupled with LC-MS technology in screening active components of TCMs, including the principle, characteristics and the research advancement.