Fluorescein-functionalized silica nanoparticles (1) were prepared by sol-gel reaction, and their optical sensing abilities were studied towards finding a new type of synthetic fluorogenic chemosensor for imaging Cu 2+ ions in living cells. Interestingly, upon addition of Cu 2+ in a H2O suspension of 1 at pH 7.4, 1 displays large chelation-enhanced quenching (CHBQ) effects with Cu2+. With the exception of Cu2+, no significant fluorescence intensity changes were observed in the experiments with the other metal ions. These findings confirm that 1 can be useful as a fluorogenic-sensing material for the selective detection of Cu2+ in the presence of other metal ions. This is a rare example of chromogenic sensing of a specific metal ion by functional inorganic nanomaterials. The emission change observed for chemosensor 1 in the presence of Cu2+ is reversible by the addition of EDTA. Furthermore, the fluorescein-functionalized silica nanoparticles act as a new type of synthetic fluorogenic chemosensor for imaging Cu2+ ions in living cells.