Proteolysis-targeting chimera (PROTAC), as an emerging treatment method, has become one of the hottest technologies in the field of new drug research with a near-20-year development. PROTAC utilizes the natural ubiquitin-protease system in cells to induce targeted protein degradation, especially for protein of interest that are difficult to target by traditional small molecules. Moreover, PROTAC is expected to solve the problem of drug resistance that often occurs with small molecule drugs. However, the excessive relative molecular weight, poor solubility and membrane permeability, and low oral absorption of PROTAC make it challenging to druggability study. Currently, take pharmacokinetic characteristics as the entry point to continuously optimize and improve, so as to accelerate the transformation of PROTAC from laboratory to clinical application. Based on the basic structure and mechanism of PROTACs, this review introduces its pharmacokinetic properties, analyzes how to design efficient and stable PROTAC molecules, summarizes its current research progress in various diseases treatments, evaluates the development prospects and limitations of PROTAC, in order to provide more references for further research and application of PROTAC.