A facile and simple route to manufacture active surfaceenhanced Raman scattering (SERS) substrate based on Ag-decorated Cu2O micro/nanospheres on Cu foil was systematically investigated. Hierarchical Cu2O micro/nanostructure transfers from CuO nanosheets and Cu(OH)2 nanowires by means of thermally reducing the oxides from Cu2+ to Cu1+ at temperature of 500 °Cunder nitrogen atmosphere. The subsequent decoration of Ag on Cu2O nanostructural substrate was carried out by means of thermal evaporator deposition. Using 4-aminothiophenol (4-ATP) as probing molecules, the SERS experiments showed that the Ag-decorated Cu2O micro/nanospheres exhibit excellent detecting performance, which could be used as effective SERS substrate for ultrasensitive detection. Additionally, these novel hierarchical SERS substrates showed good reproducibility and a linear dependence between analyte concentrations and intensities, revealing the advantage of this method for easily scale-up production.