Nanophosphors are light-emitting materials with stable optical properties that represent promising tools for bioimaging. The synthesis of nanophosphors, and thus the control of their surface properties, is, however, challenging. Here, flame aerosol technology is exploited to generate Tb-activated Y(2)O(3) nanophosphors (∼25 nm) encapsulated in situ by a nanothin amorphous inert SiO(2) film. The nanocrystalline core exhibits a bright green luminescence following the Tb(3+) ion transitions, while the hermetic SiO(2)-coating prevents any unspecific interference with cellular activities. The SiO(2)-coated nanophosphors display minimal photobleaching upon imaging and can be easily functionalized through surface absorption of biological molecules. Therefore, they can be used as bionanoprobes for cell detection and for long-term monitoring of cellular activities. As an example, we report on the interaction between epidermal growth factor (EGF)-functionalized nanophosphors and mouse melanoma cells. The cellular uptake of the nanophosphors is visualized with confocal microscopy, and the specific activation of EGF receptors is revealed with biochemical techniques. Altogether, our results establish SiO(2)-coated Tb-activated Y(2)O(3) nanophosphors as superior imaging tools for biological applications.