The　emergence　of　acquired　resistance　to　epidermal　growth　factor　receptor　tyrosine　kinase　inhibitors　(EGFR-TKIs)　poses　formidable　obstacles　to　non-small　cell　lung　cancer　(NSCLC)　therapy.　Real-time　monitoring　of　the　efficacy　of　EGFR-TKIs　to　avoid　invalid　treatment　remains　a　great　challenge.　Herein,　we　rationally　designed　a　EGFR-TKI-modified　liposomal　complex　co-loaded　with　a　iodine-containing　contrast　agent　ioversol　(IOV)　and　a　photosensitizer　indocyanine　green　(ICG),　namely　ELIG,　for　simultaneous　EGFR-TKI-mediated　computed　tomography/fluorescence　dual-modal　imaging　to　monitor　drug　resistance　during　the　treatment,　and　combined　photodynamic　therapy　(PDT)　and　photothermal　therapy　(PTT)　to　reverse　drug　resistance.　ELIG　exhibited　good　physicochemical　properties,　favorable　photothermal　effects,　and　high　singlet　oxygen　production.　ELIG　can　protect　ICG　and　IOV　from　rapid　degradation　and　prolong　the　circulation　time.　In　addition,　ELIG　had　a　great　ability　to　recognize　drug-sensitive　EGFR-mutated　NSCLC　cells,　and　could　monitor　the　changes　in　the　intracellular　amounts　of　the　imaging　agents　to　detect　the　drug　resistance　and　predict　the　efficacy　during　the　treatments.　Additionally,　the　heavy　atom　effect　of　IOV　can　increase　the　PDT　effect　of　ICG　obviously.　With　808　nm　laser　irradiation,　ELIG　showed　satisfactory　anticancer　effects　to　reverse　drug　resistance　by　the　synergism　of　PDT　and　PTT　in　vitro　and　in　vivo.　Hence,　this　work　holds　great　promise　for　providing　a　new　idea　and　an　effective　strategy　for　predicting　and　managing　the　efficacy　of　EGFR-TKIs.　©　2024　Elsevier　Ltd