Magnetic CuO nanosheet (Mag-CuO), as a cheap, stable, efficient and easily separated peroxymonosulfate (PMS) activator, was prepared by a simple one-step precipitation method for the removal of organic compounds from salt-containing wastewater. The experiments showed that the removal efficiencies of various organic pollutants including Acid Orange 7, Methylene Blue, Rhodamine B and atrazine in a high-salinity system (0.2 mol/L Na2SO4) with the Mag-CuO/PMS process were 95.81%, 74.57%, 100% and 100%, respectively. Meanwhile, Mag-CuO still maintained excellent catalytic activity in other salt systems including one or more salt components (NaCl, NaNO3, Na2HPO4, NaHCO3). A radical-quenching study and electron paramagnetic resonance analysis confirmed that singlet oxygen (1O2) was the dominant reactive oxygen species for the oxidation of organic pollutants in high-salinity systems, which is less susceptible to hindrance by background constituents in wastewater than radicals (•OH or SO4•-). The surface hydroxylation of the catalyst and catalytic redox cycle including Cu and Fe are responsible for the generation of 1O2. The developed Mag-CuO catalyst shows good application prospects for the removal of organic pollutants from saline wastewater.