Bioaccumulation of nanoplastic particles draws increasing attention regarding environmental sustainability and biosafety. How nanoplastic particles interact with cellular milieu still remains elusive. Herein, we exemplify a general approach to profile the composition of “protein corona” interacting with nanoparticles via the photocatalytic protein proximity labeling method. To enable photocatalytic proximity labeling of proteome interacting with particles, iodine substituted BODIPY (I-BODIPY) is selected as the photosensitizer and covalently conjugated onto amino-polystyrene nanoparticle as a model system. Next, selec-tive proximity labeling of interacting proteins is demonstrated using I-BODIPY labeled nanoplastic particles in both E. coli lysate and live AML 12 cells. Mechanistic studies reveal the covalent modifications of proteins by amino-alkyne substrate is conducted via reactive oxygen species (ROS) photosensitization pathway. Further proteomic analysis uncovers that mitochon-dria-related proteins are intensively involved in protein corona, indicating substantial interactions between nanoplastic particles and mitochondria. In addition, proteostasis network components are also identified accompanied with consequent cellular pro-teome aggregation confirmed by fluorescence imaging. Together, this work exemplifies a general strategy to interrogate the composition of protein corona of nanomaterials by grafting them photo-oxidation property to enable photocatalytic protein proximity labeling function.