Elucidating the generation mechanism of reactive oxygen species (ROS) is essential for advanced oxidation processes with respect to environmental and biological sciences. Herein, self-generation of ROS such as hydroxyl radicals (·OH), superoxide radicals (O) and singlet oxygen (O) from the interaction between multi-layered flowerlike MoS nanosheets and HO is presented. The results demonstrate that HO can exfoliate multi-layered MoS into quantum dots and promote a 2H to 1 T phase change accompanied by the dissolution of MoS to produce H, MoO and SO. Electron spin resonance (ESR) spectroscopy confirm the production of ·OH, superoxide radicals O and O in the MoS/HO system. The calculation data based on density functional theory (DFT) indicate that the 1 T-MoS can lower the free energy profiles for stepwise catalytic decomposition of HO to produce ROS as compared to 2H-MoS.