oligonucleotide‐based proteolysis‐targeting chimeras (O'PROTACs), which employ unique DNA sequences as natural “ligand” of targeting proteins, are developed to effectively destruct lymphoid enhancer‐binding factor 1 (LEF1) and ETS‐related gene (ERG) and inhibit prostate cancer cell growth. Here, LEF1 is linked to Familial prostate cancer.