The　development　of　smart　platform　with　accurate,　inexpensive　and　reliable　detection　of　single-nucleotide　polymorphisms　(SNPs)　has　long　been　concerned　in　the　fields　of　medical　diagnosis　and　basic　research.　Here,　we　present　a　ligation　chain　reaction　(LCR)-based　sensing　system　for　the　cost-effective　screening　of　SNPs　by　simply　conducting　DNA　melting　analysis.　No　chemical　modification　is　required　and　the　signaling　operation　is　accomplished　in　homogeneous　solution,　circumventing　the　complex　modification　process　and　possibly　compromised　enzymatic　activity　associated　with　heterogeneous　materials,　such　as　quantum　dot　(QD)　and　gold　nanoparticle　(GNP).　Due　to　the　enzymatic　catalysis　and　high　fidelity　of　ligase,　the　system　is　capable　of　executing　signal　amplification,　providing　a　high　sensitivity　and　selectivity.　KRAS　gene　is　easily　recognized　and　the　site-specific　mutation　of　guanine　(G)　to　adenine　(A),　thymine　(T)　or　cytosine　(C)　is　accurately　screened.　Moreover,　the　excellent　reliability　was　demonstrated　by　blind　test　and　recovery　test.　LCR-based　signaling　mechanism　was　further　used　to　develop　the　biocomputing　security　system,　and　two　logic　gates　consisting　of　four　single-stranded　DNAs　(ssDNAs)　offer　a　double　insurance　to　protect　the　information　against　illegal　invasion,　guaranteeing　the　reliability　of　output　information.　Once　in　the　absence　of　one　essential　factor,　the　security　system　was　always　locked　regardless　of　target　key,　serving　as　a　novel　strategy　to　ensure　the　safety　of　output　information　at　molecular　level.　As　a　proof-of-concept　scheme,　this　contribution　introduces　new　insight　into　the　development　of　DNA　security　systems　and　the　exploitation　of　powerful　signal　transduction　strategy　suitable　for　rapid　and　convenient　disease　diagnosis.　©　2020　Elsevier　B.V.