Abstract: A simple in-situ reduction strategy was developed to synthesize copper nanoclusters-loaded and organosilica-stabilized polystyrene-b-polyacrylic acid (PS-b-PAA) micelles (Cu-POMs). Firstly, the structure of PS-b-PAA micelles were fixed by MPTMS to obtain thiol-modified organosilica micelles (POMs). Subsequently, considering the coordination ability of copper ions with thiol groups, Cu-POMs were successfully prepared. The morphology and hydrodynamic size of Cu-POMs were detected by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. Raman spectroscopy was used to detect the functional groups of Cu-POMs. The valence of Cu in Cu-POMs was analyzed by X-ray photoelectron spectroscopy (XPS). The stability of Cu-POMs in simulating physiological conditions was investigated by DLS. Besides, the ability to generate hydroxyl radical (•OH) through Fenton-like reaction of Cu-POMs was verified by the methylene blue (MB) degradation experiment. Finally, the cytotoxicity experiments were used to evaluate biosafety and killing effect on tumor cells of Cu-POMs. The results showed that Cu-POMs had pH-responsive and glutathione (GSH) depletion properties, which could effectively catalyze H₂O₂ to generate highly cytotoxic •OH. Consequently, it is highly expected that Cu-POMs can be used as a new class of nano-Fenton reagents for the efficient and safe tumor treatment.