A simple aqueous approach for synthesizing biocompatible red and near-infrared (NIR) emitting Ag2S quantum dots (QDs) at low temperature without a required oxygen-free process has been developed. The fluorescence of the obtained red emitting Ag2S QDs could be selectively quenched by Cu2+. Based on this, a novel Ag2S QD based fluorescent sensor for highly selective and sensitive detection of Cu2+ was developed. This method showed a low limit of detection (LOD) of 27.6 nM for Cu2+ sensing in a wide linear range concentration of 25 nM-10 μM. The quenching mechanism was discussed by the time-resolved photoluminescence, absorption spectra, TEM and energy-dispersive X-ray (EDX) results. Cation exchange of Ag2S QDs between Cu(ii) and Ag(i), and dynamic quenching due to excited state electron transfer from Ag2S QDs to Cu2+ were considered to be the quenching mechanism. Furthermore, to understand the interaction between Ag2S QDs and Cu2+, the thermodynamic process was investigated by means of isothermal titration calorimetry (ITC). The values of ΔH, ΔS and ΔG were calculated from the ITC results to be -79.43 kJ mol-1, -142.18 J K-1 mol-1 and -37.06 kJ mol-1, respectively. The Ag2S QD based Cu2+ detection had advantages of nontoxicity, fast response, high sensitivity and selectivity, wide linear range and easy preparation.