Herein, we report a facile one-pot method for the synthesis of orange/red-emitting fluorescent copper nanoclusters (Cu NCs), in which bovine serum albumin (BSA) served as the capping scaffold (Cu NCs@BSA) and hydroxylamine hydrochloride (NH2OH ⋅ HCl) as the reducing agent. To the best of our knowledge, this is the first time to adopt this mild reductant to synthesize fluorescent Cu NCs. The as-prepared Cu NCs@BSA exhibits strong orange or red fluorescence at room temperature depending on the synthesis process, and the maximum excitation and emission peaks were at 355 nm and 615 nm, 395 nm and 645 nm, respectively. Synthesis conditions including the amounts of NH2OH ⋅ HCl, the selection of reducing agent, the molar ratio of BSA/Cu(NO3)2, the pH... value, the reaction temperature, the reaction time, and various kinds of Cu sources have been systematically studied. Importantly, these Cu NCs exhibit excellent stability for at least 2 months when stored at 4 ∘ C in the dark, and they also show strong oxidation resistance toward H2O2. Moreover, the prepared Cu NCs have been successfully applied to sensitively and selectively sensing Hg 2 + without suffering any interference from other metal ions and anions.