The fabrication of photo-degradable, proteinpolyelectrolyte complex (PPC)-coated, mesoporous silica nanoparticles (MSNs) and their controlled co-release of protein and model drugs is reported. Random copolymers composed of oligo(ethylene glycol) monomethyl ether methacrylate (OEGMA), and a photolabile o-nitrobenzyl-containing monomer, 5-(2-(dimethylamino)ethoxy)-2-nitrobenzyl methacrylate (DENBMA), are first anchored onto the MSNs and then quaternary aminated, to obtain positively charged P(OEGMA-co-TENBMA) which exhibits photo-induced charge conversion characteristics. PPCs consisting of P(OEGMA-co-TENBMA) and the protein bovine serum albumin (BSA) are utilized as capping agents for the nanopores of the MSNs. Upon UV irradiation, charge conversion of P(OEGMA-co-TENBMA) can lead to the disruption of PPCs on MSNs and co-release of BSA and rhodamine B by electrostatic repulsion.