In this paper we describe the preparation of fluorescent mesoporous silica nanoparticles (MSNs) for traceable drug delivery systems. The nanoparticles were prepared following a sol–gel procedure, incorporating a modified perylenediimide dye in the silica structure. Transmission electron microscopy and scanning electron microscopy show that the nanoparticles are monodispersed, with a spheroid shape and a raspberry-type surface morphology. The hybrid MSNs are robust, maintaining the mesoporous structure after template removal, with a pore diameter above 2 nm. A polymer shell was synthesized from the external surface of the hybrid nanoparticles by atom transfer radical polymerization, showing temperature-switchable collapsed/expanded conformation control. The fluorescent properties of the perylenediimide dye incorporated in the MSN pore walls are intact, and internalization in HEK293 cells shows that the nanoparticles are efficiently dispersed in the cytosol. These results show that the mesoporous fluorescent hybrid nanoparticles are an excellent platform for development of a traceable drug delivery system.