Due　to　fascinating　properties,　such　as　structural　stability,　excellent　biocompatibility,　and　desirable　drug　delivery　efficiency,　DNA　dendrimer　nanostructures　are　attracting　growing　scientific　interest　in　biomedical　diagnosis　and　therapy.　However,　they　are　lagging　behind　in　clinical　development　because　of　complicated　design,　complicated　assembly　process,　inconvenience　of　modification　with　targeting　ligands,　and　limited　drug　loading　capability.　In　this　study,　via　introducing　three　identical　palindromic　fragments,　a　rotationally-symmetric　Y-shaped　structural　unit　(SYSU)　is　designed　for　constructing　the　simplest　programmable　DNA　dendrimer　(PDD)　and　nondeformable　DNA　hydrogel　by　one-pot　self-assembly.　The　assembly　efficiency　is　almost　up　to　100%.　After　the　surface　is　functionalized　with　aptamers　with　the　help　of　two　leg-shaped　retaining　screws,　PDD　is　developed　into　a　highly-precise　drug　delivery　carrier.　The　two-point-fixed　aptamers　display　a　rigidified　structure　so　that　they　can　resist　the　attack　of　endogenous　nucleases　and　possess　a　persistent　cell-targeting　ability　in　living　organisms.　PDD-aptamer　is　almost　not　degraded　upon　24　h　incubation　in　a　complex　biological　environment　and　holds　up　to　1500　times　higher　cargo　holding　capability　(76　700　Dox　per　particle).　After　intravenous　administration　into　tumor-bearing　mice,　Dox-PDD-sgc8　can　cause　largely　negative　growth　in　tumor　volume　without　any　notable　systemic　toxicity,　manifesting　the　enormous　potential　for　precision　cancer　therapy.