The second near-infrared window emission (1.0-1.7 μm, NIR-II) has received extensive attention with the advantages of negligible tissue scattering, reduced autofluorescence, and less background noise. Here a novel analysis platform based on quantum dots (QDs) for highly selective detection of Zn2+ and Cd2+ with an enhanced NIR-II fluorescence is reported for the first time. We have developed a facile two-step route to synthesize the water-soluble Ag2S QDs, constituting of a green hydrothermal process and followed surface ligands exchange. Surface passivation was proposed to be the mechanism for the enhanced fluorescence. The added Zn2+ or Cd2+ could react with the surface thioglycollic acid to form Zn-thiol or Cd-thiol complex passivation shell, which restored surface defects and suppressed nonradiative recombination pathway. The detection platform exhibited a linear relationship between the ion concentrations and enhanced fluorescence and had a detection limit as low as 760 nM for Zn2+ and 546 nM for Cd2+ at pH = 7.4. Furthermore, the as-synthesized Ag2S QDs showed good robustness in real sample matrix and were demonstrated to be able to detect exogenous Zn(II) in cells. These properties suggest potential applications of detection of Zn2+ in biology and Cd2+ in environment via the NIR-II fluorescent Ag2S QDs.