PROTAC PD-1/PD-L1 degrader-1, a PD-1/PD-L1 degrader, inhibits PD-1/PD-L1 interaction with an IC50 of 39.2 nM. PROTAC PD-1/PD-L1 degrader-1 significantly restores the immunity repressed in a co-culture model of Hep3B/OS-8/hPD-L1 and CD3 T cells. PROTAC PD-1/PD-L1 degrader-1 moderately reduces the protein levels of PD-L1 in a lysosome-dependent manner.