The　endoplasmic　reticulum　(ER),　as　the　largest　organelle　in　eukaryotic　cells,　plays　complex　but　pivotal　roles　in　multiple　intracellular　metabolic　functions,　including　biosynthesis,　sensing,　and　signal　transduction,　especially　in　proteins　folding　and　post-translation　modification.　The　ER　is　regarded　as　a　promising　target　for　anticancer　therapy.　Based　on　previous　tumor-targeted　photodynamic　therapy　(PDT),　we　chemically　modified　the　phthalocyanine-based　photosensitizer　molecule　with　the　small　molecular　anticancer-targeting　drug　erlotinib　and　the　ER-targetable　moiety　methyl　sulfonamide　to　develop　an　advanced　photosensitizer　EB-ER-Pc　that　can　specifically　target　the　subcellular　organelle　ER　of　EGFR-overexpressing　cancer　cells.　The　in　vitro　experiments　show　that　the　dual-target　photosensitizer　EBER-Pc　can　generate　ROS　in　situ　in　the　ER　of　the　tumor　target　region　to　induce　ER　stress,　upregulate　Ca2+　ion　level,　and　decrease　mitochondrial　membrane　potential　(MMP)　to　mediate　cancer　cells　death　and　ablation.　The　results　suggest　that　EB-ER-Pc　is　a　promising　candidate　for　effective　photodynamic　cancer　therapy.　(C)　2019　Elsevier　Masson　SAS.　All　rights　reserved.