In this work, an “on‐off‐on” nanoprobe for specific detection of Cd2+ was constructed using N‐acetyl‐l‐cysteine (NAC)‐modified CdSe quantum dots (QDs). The prepared CdSe QDs exhibit characteristic green fluorescence. The adsorbed S2− on the surface of CdSe QDs leads to dangling bonds and causes the fluorescence quenching of QDs, where the fluorescence of the system turns “off“. When Cd2+ exists, it can react with the adsorbed S2− to form CdS shell, resulting in the fluorescence enhancement of CdSe QDs, where the fluorescence of the system turns “on”. Due to the similar lattice structure between CdSe and CdS, CdSe/CdS can be produced by shell deposition, while self‐nucleation of metal sulfide is observed in the presence of other metal ions. Thus, the developed nanoprobe shows high selectivity for Cd2+. Under the optimum sensing conditions, the fluorescence sensing signal of CdSe QDs depends linearly on the Cd2+ in the range of 0.2–9 μM. The limit of detection (LOD) and limit of quantification (LOQ) of this nanoprobe is 27 nM and 90 nM, respectively. Furthermore, the proposed nanoprobe can monitor Cd2+ in drinking water with a recovery rate between 95.82 % and 102.00 %, indicating its good practicability and applicability for real sample analysis.