DNA　nanostructures　have　shown　potential　in　cancer　therapy.　However,　their　clinical　application　is　hampered　by　the　difficulty　to　deliver　them　into　cancer　cells　and　susceptibility　to　nuclease　degradation.　To　overcome　these　limitations,　we　report　herein　a　periodically　ordered　nick-hidden　DNA　nanowire　(NW)　with　high　serum　stability　and　active　targeting　functionality.　The　inner　core　is　made　of　multiple　connected　DNA　double　helices,　and　the　outer　shell　is　composed　of　regularly　arranged　standing-up　hairpin　aptamers.　All　termini　of　the　components　are　hidden　from　nuclease　attack,　whereas　the　target-binding　sites　are　exposed　to　allow　delivery　to　the　cancer　target.　The　DNA　NW　remained　intact　during　incubation　for　24　h　in　serum　solution.　Animal　imaging　and　cell　apoptosis　showed　that　NWs　loaded　with　an　anticancer　drug　displayed　long　blood-circulation　time　and　high　specificity　in　inducing　cancer-cell　apoptosis,　thus　validating　this　approach　for　the　targeted　imaging　and　therapy　of　cancers.　©　2020　Wiley-VCH　GmbH