Polyhedral oligomeric silsesquioxane (POSS) molecules have a distinct nanostructure, consisting of an inner inorganic cage core of silicon and oxygen atoms and an outer shell of organic functional groups. The unique structure of POSS molecules containing reactive functionalities and their superior biocompatibility make them suitable drug-delivery carriers. In the present study, we prepared p 18-4/chlorin e6 (Ce6)-conjugated POSS (PPC) nanoparticles for improving the targeting ability of Ce6 to breast cancer cells. To fabricate PPC nanoparticles, p 18-4 was first covalently conjugated on OctaMaleamicacid POSS (OM-POSS), and subsequently, amino-terminated Ce6 was introduced. To verify the availability of the PPC nanoparticles for cancer therapy, their physicochemical properties, including morphology, chemical structure, and particle size, were systematically characterized. The cellular uptake, phototoxicity, and targeting ability of the PPC nanoparticles were assessed using a human breast cancer cell line MDA-MB-231. In addition, PPC nanoparticles was injected intravenously into tumor-bearing mice to evaluate in vivo biodistribution and PDT efficacy.