Nucleic acid drugs, which trigger gene silencing by hybridizing with target genes, have shown great potential in targeting those undruggable targets. However, most of the existing nucleic acid drugs are only sequence specific for target genes and lack cellular or tissue selectivity, which challenges their therapeutic safety. Here, the study proposes a tumor cell-specific gene silencing strategy by using hairpin DNA oligonucleotides to trigger target RNA degrading by highly expressed endogenous flap endonuclease 1 (FEN1) in tumor cells, for selective tumor therapy. Using Kirsten rat sarcoma viral oncogene homolog (KRAS