DNA　is　a　versatile　scaffold　for　the　assembly　of　multifunctional　nanostructures,　and　potential　applications　of　various　DNA　nanodevices　have　been　recently　demonstrated　for　disease　diagnosis　and　treatment.　In　the　current　study,　a　powerful　cascade　DNA　nanomachine　was　developed　that　can　execute　the　exponential　amplification　of　p53　tumor　suppressor　gene.　During　the　operation　of　the　newly-proposed　DNA　nanomachine,　dual-cyclical　nucleic　acid　strand-displacement　polymerization　(dual-CNDP)　was　ingeniously　introduced,　where　the　target　trigger　is　repeatedly　used　as　the　fuel　molecule　and　the　nicked　fragments　are　dramatically　accumulated.　Moreover,　each　displaced　nicked　fragment　is　able　to　activate　the　another　type　of　cyclical　strand-displacement　amplification,　increasing　exponentially　the　value　of　fluorescence　intensity.　Essentially,　one　target　binding　event　can　induce　considerable　number　of　subsequent　reactions,　and　the　nanodevice　was　called　cascade　DNA　nanomachine.　It　can　implement　several　functions,　including　recognition　element,　signaling　probe,　polymerization　primer　and　template.　Using　the　developed　autonomous　operation　of　DNA　nanomachine,　the　p53　gene　can　be　quantified　in　the　wide　concentration　range　from　0.05　to　150　nM　with　the　detection　limit　of　50　pM.　If　taking　into　account　the　final　volume　of　mixture,　the　detection　limit　is　calculated　as　lower　as　6.2　pM,　achieving　an　desirable　assay　ability.　More　strikingly,　the　mutant　gene　can　be　easily　distinguished　from　the　wild-type　one.　The　proof-of-concept　demonstrations　reported　herein　is　expected　to　promote　the　development　and　application　of　DNA　nanomachine,　showing　great　potential　value　in　basic　biology　and　medical　diagnosis.　(C)　2015　Elsevier　B.V.　All　rights　reserved.