Abstract: The proteolysis targeting chimera（PROTAC） technology bridges the protein of interest（POI） and the E3 ubiquitin ligase through a heterobifunctional molecule, thereby utilizing the ubiquitin-proteasome system to achieve the specific POI degradation. However,PROTACs face limitations of uneven tissue distribution of exogenous E3 ubiquitin ligases and drug resistance in applications. In contrast,the chaperone-mediated protein degrader（CHAMP） technology innovatively leverages the highly expressed heat shock protein 90（HSP90）system in tumor cells. Through either endogenous E3 ubiquitin ligases-mediated ubiquitination or the chaperone-mediated autophagy pathway, it achieves the selective POI degradation, enhancing the specificity of degradation. In preclinical studies, CHAMP molecules have demonstrated favorable blood-brain barrier（BBB） permeability and potent antitumor efficacy. Nevertheless, the broad physiological functions of HSP90 may trigger off-target effects, and the relatively large molecular weight of CHAMPs may pose pharmacokinetic challenges. This review highlights the innovative mechanisms of CHAMP technology and its advantages over PROTAC in tissue specificity and drug resistance, and looks forward to its potential in the treatment of tumors.