The detection and imaging of intracellular copper ions (Cu2+) play a crucial role in understanding their physiological implications and their involvement in various cellular processes. This study focuses on the synthesis and characterization of water-soluble near-infrared fluorescent CIS/ZnS core–shell quantum dots (QDs) with excellent biocompatibility and stability. The QDs exhibit exceptional selectivity and sensitivity for Cu2+ detection, allowing for precise quantification of Cu2+ content within biological systems. Furthermore, Co-incubation of the QDs with HeLa cells demonstrates their impressive cellular imaging capabilities, facilitated by fluorescence bursts in response to changing Cu2+ content. Overall, our proposed QDs are of great significance in advancing the research and application of near-infrared semiconductor quantum dots in biomedicine, and their near-infrared fluorescence properties and high fluorescence quantum yield (34.48 %) make them very advantageous for the precise detection of intracellular Cu2+ and cell fluorescence imaging. This research contributes to the understanding of copper ion dynamics within cells and opens avenues for further exploration of its role in cellular physiology.