As　DNA　is　employed　to　serve　as　a　smart　building　block,　an　increasing　interest　has　been　devoted　to　the　development　of　different　DNA-based　machines　for　the　specific　purpose,　for　example,　the　exploration　of　inter-　or　intramolecular　interaction.　In　the　current　contribution,　we　developed　an　intelligent　DNA　machine　and　its　operation　can　be　designed　to　execute　the　ultrasensitive　calorimetric　detection　of　target　nucleic　acids.　The　DNA　machine　consists　of　a　hairpin　probe　(HP)　and　an　assistant　template　(AT).　Using　p53　gene　as　the　target　model　to　trigger　the　molecular　machine　operation,　cyclic　nucleic　acid　strand　displacement　polymerization　(CNDP)　was　specifically　induced,　leading　to　the　DNAzyme　mediated　catalytic　reaction　for　signal　readout.　Specifically,　with　the　help　of　polymerase　and　nickase,　one　target　molecule　was　able　to　drive　DNA　nano-mechanical　devices　one-by-one　through　the　hybridization/polymerization　displacement　cycles,　and　every　initiated　machine　continued　to　operate,　causing　the　dramatic　accumulation　of　G-quadruplex-contained　products.　The　G-quadruplex　structure　after　binding　to　hemin　could　act　as　a　horseradish　peroxidase　(HRP)-mimicking　DNAzyme　and　catalyzed　the　oxidation　of　2,2＇-azino-bis(3-ethylbenzothiazoline-6-sulfonic　acid)　(ABTS)　by　H2O2.　As　a　result,　an　enhanced　color　change　could　be　detected　because　of　the　generation　of　oxidation　product　ABTS(circle)(+).　In　this　way,　the　DNA　machine　has　no　any　signal　loss　and　enables　the　quantitative　measurement　of　p53　DNA　with　a　detection　limit　of　10　fM,　indicating　great　promise　for　unique　application　in　biomedical　research　and　early　clinical　diagnosis.　(C)　2015　Elsevier　B.V.　All　rights　reserved.