The　outcome　of　molecular　targeted　therapies　is　restricted　by　the　ambiguous　molecular　subtypes　of　nonsmall　cell　lung　cancer　(NSCLC),　which　are　difficult　to　be　defined　with　druggable　mutations,　and　the　inevitable　emergence　of　drug-resistance.　Here　we　used　the　Cu-catalyzed　click　chemistry　to　synthesize　a　chitosan-based　self-assembled　nanotheranostics　(CE7Ns)　composed　of　a　near-infrared　(NIR)　fluorescent　photosensitizer　Cy7　and　molecular　targeted　drug　erlotinib.　The　well-characterized　CE7Ns　can　release　erlotinib　and　Cy7　fast　under　acidic　condition　in　the　presence　of　lysozyme,　distinguish　three　molecular　subtypes　of　NSCLC,　and　specifically　bind　to　the　erlotinib-sensitive　epidermal　growth　factor　receptor　(EGFR)-mutated　PC-9　cells.　The　uptake　of　CE7Ns　is　much　more　in　PC-9　cells　than　in　other　NSCLC　cells,　thus　generating　a　notable　fluorescence　signal　in　PC-9　cells.　Upon　NIR　irradiation,　Cy7　in　CE7Ns　produces　high　reactive　oxygen　species　in　PC-9　cells.　The　synergistic　effect　between　erlotinib-targeted　therapy　and　photodynamic　therapy　significantly　up-regulates　cancer　suppressor　p53　and　inhibits　Survivin,　which　results　in　more　apoptosis　and　cell　cycle　arrest.　Upon　intravenous　administration,　the　erlotinib-guided　CE7Ns　significantly　accumulate　in　PC-9-seeded　mouse　lungs　and　produce　strong　fluorescence.　Upon　NIR　irradiation,　CE7Ns　significantly　inhibit　the　subcutaneously　implanted　PC-9　tumor　growth.　This　study　provides,　for　the　first　time,　a　novel　strategy　to　synthesize　a　multifunctional　theranostic　entity　to　simultaneously　distinguish　and　image　druggable　mutations　and　combine　targeted　therapy　with　photodynamic　therapy　to　overcome　drug　resistance.