Western blotting confirmed that c(RGDyK)-Tz can bioorthogonally activate inactive prodrugs to promote BRD4 degradation in HeLa cells through the ubiquitin–proteasome pathway, and the selectivity of BRD4 degradation in other cancer cells with high αvβ3 integrin expression validated the universality of this strategy. Here, BRD4 is linked to cancer.