In this paper, ZnSe nanoparticles, which were modified with mercaptoacetic acid (MAA), worked as novel fluorescence sensors for the quantitative determination of copper(II) and nickel(II). Under the optimal conditions, the fluorescence intensities of functionalized ZnSe nanoparticles were quenched by the addition of copper(II) or nickel(II) ions, there were linear relationships between the relative fluorescence intensity (logF(0)/F) and the concentration in the range of 140-2,000 microg/L for copper(II) (R = 0.9973) and 30-1,000 microg/L for nickel(II) (R = 0.9992), the limits of detection were 50 microg/L and 5 microg/L, respectively.