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A facile strategy for designing a glutathione-capped Mn-doped CdS/ZnS/CdS core/shell/shell QD-based fluorescent nanosensor has been developed for rapid, selective, and ultrasensitive detection of Cu 2+ . In this nanosensor, glutathione provided the binding and recognition sites for Cu 2+ , accumulating Cu 2+ on the QD surface. The energy transfer pathway from the host to the Mn dopant was sensitive to the interferences from non-radiative recombination pathways caused by Cu 2+ , resulting in photoluminescence quenching. The nanosensor responsed to Cu 2+ within one minute and exhibited good selectivity to Cu 2+ over other metal ions and good linear correlation over the concentration range of 1 nM to 100 nM, with a detection limit as low as 0.74 nM. Moreover, this nanosensor avoids the self-quenching problem and autofluorescence in biosystems due to the substantial Stokes shift and long lifetime, and thus can be used to monitor Cu 2+ in living cells.