The　sensitive　detection　of　tumor　proto-oncogenes　is　indispensable　because　the　early　diagnosis　and　accurate　treatment　of　genetic　diseases　is　the　key　guarantee　of　patients＇　health.　In　this　study,　we　proposed　a　novel　palindromic　molecular　beacon　(PMB)　that　it　bases　on　the　signal　amplification　strategy　for　ultrasensitive　detection　of　Kras　gene　codon　12.　PMB　is　designed　to　have　two　palindromic　fragments　at　its　two　ends,　one　of　which　is　locked　via　folding　into　a　hairpin　structure　and　the　other　promotes　the　formation　of　PMB　duplex　via　intermolecular　self-hybridization.　Target　DNA　can　hybridize　to　the　loop　portion　of　PMB　and　release　the　palindromic　fragment　at　the　3’　end.　Within　the　PMB　duplex,　the　two　palindromic　fragments　released　hybridize　with　each　other　and　serve　as　polymerization　primer　responsible　for　the　strand-displacement　amplification　(SDA).　Namely,　hybridized　target　DNA　can　be　displaced　and　initiates　the　next　round　of　reactions,　making　the　polymerization/displacement/hybridization　process　go　forward　circularly.　As　a　result,　a　large　number　of　polymerization　products　are　produced,　dramatically　enhancing　optical　signal.　Because　primer　hybridization　and　polymerization-based　displacement　occur　within　PMB　duplex,　the　reaction　process　is　called　intramolecular　strand-displacement　amplification　(ISDA).　Via　utilizing　the　newly-proposed　PMB-based　ISDA　strategy,　the　target　K-ras　gene　could　be　detected　down　to　10　pM　with　a　wide　response　range　of　1　×　10−11-1.5　×　10−7　M,　and　point　mutations　are　easily　distinguished,　realizing　the　ultrasensitive,　highly　selective　detection　of　K-ras　gene.　This　impressive　sensing　paradigm　demonstrates　a　new　concept　of　signal　amplification　for　the　detection　of　disease-related　genes　only　via　using　a　simple　way　to　efficiently　amplify　optical　signal.　©　2019　Elsevier　B.V.