Acquired　resistance　to　epidermal　growth　factor　receptor　tyrosine　kinase　inhibitors　(EGFR-TKIs)　is　inevitably　developed　in　non-small　cell　lung　cancer　(NSCLC)　and　the　major　cause　of　resistance　to　first-generation　EGFR-TKIs　is　the　T790M　secondary　mutation.　Real-time　detection　of　the　acquired　T790M　mutation　to　avoid　futile　treatment　and　timely　adjust　the　therapeutic　interventions　remains　a　great　challenge.　Molecular　beacon　(MB)　could　achieve　real-time　detection　of　point　mutation　and　the　fluorophores　located　at　the　terminal　of　MB　could　be　activated　for　photodynamic　therapy　(PDT).　Herein,　a　multifunctional　nanoplatform　CQEM　based　on　erlotinib　and　tertiary　amine　dual-fabricated　chitosan　(CQE)　loaded　with　cyanine　dyes-labeled　MB　was　prepared　for　simultaneous　detection　of　the　degree　of　T790M　mutation　in　real-time　and　reversal　of　the　resistance　by　PDT.　CQE　could　protect　MB　against　DNase　I　digestion　and　CQEM　could　achieve　real-time　sensing　of　T790M　mutation　during　the　course　of　EGFR-TKI　treatments.　With　808　nm　laser　irradiation,　CQEM　showed　substantial　therapeutic　efficiency　and　could　overcome　the　acquired　resistance　by　the　synergism　of　targeted　molecular　therapy　and　dual-cyanine　dyes-mediated　PDT.　Thus,　the　CQEM　nanoplatform　could　be　an　auspicious　tool　for　individualized　accurate　therapy　of　NSCLC　by　real-time　detection　and　management　of　the　efficacy　of　EGFR-TKIs.　©　2023　Elsevier　B.V.