The　sensitive　detection　of　cancer-related　genes　is　of　great　significance　for　early　diagnosis　and　treatment　of　human　cancers,　and　previous　isothermal　amplification　sensing　systems　were　often　based　on　the　reuse　of　target　DNA,　the　amplification　of　enzymatic　products　and　the　accumulation　of　reporting　probes.　However,　no　reporting　probes　are　able　to　be　transformed　into　target　species　and　in　turn　initiate　the　signal　of　other　probes.　Herein　we　reported　a　simple,　isothermal　and　highly　sensitive　homogeneous　assay　system　for　tumor　suppressor　p53　gene　detection　based　on　a　new　autonomous　DNA　machine,　where　the　signaling　probe,　molecular　beacon　(MB),　was　able　to　execute　the　function　similar　to　target　DNA　besides　providing　the　common　signal.　In　the　presence　of　target　p53　gene,　the　operation　of　DNA　machine　can　be　initiated,　and　cyclical　nucleic　acid　strand-displacement　polymerization　(CNDP)　and　nicking/polymerization　cyclical　amplification　(NPCA)　occur,　during　which　the　MB　was　opened　by　target　species　and　cleaved　by　restriction　endonuclease.　In　turn,　the　cleaved　fragments　could　activate　the　next　signaling　process　as　target　DNA　did.　According　to　the　functional　similarity,　the　cleaved　fragment　was　called　twin　target,　and　the　corresponding　fashion　to　amplify　the　signal　was　named　twin　target　self-amplification.　Utilizing　this　newly-proposed　DNA　machine,　the　target　DNA　could　be　detected　down　to　0.1　pM　with　a　wide　dynamic　range　(6　orders　of　magnitude)　and　single-base　mismatched　targets　were　discriminated,　indicating　a　very　high　assay　sensitivity　and　good　specificity.　In　addition,　the　DNA　machine　was　not　only　used　to　screen　the　p53　gene　in　complex　biological　matrix　but　also　was　capable　of　practically　detecting　genomic　DNA　p53　extracted　from　A549　cell　line.　This　indicates　that　the　proposed　DNA　machine　holds　the　potential　application　in　biomedical　research　and　early　clinical　diagnosis.　(C)　2018　Elsevier　B.V.　All　rights　reserved.