Cu with variable weight loading (1-5 wt%) was introduced to 5 wt% Zn mixed mesostructured silica nanoparticles (MSN) via an electrochemical method to synthesize CuO-ZnO/MSN (C-ZM) catalysts. The physicochemical properties of the catalysts were characterized by XRD, FTIR, XPS, N-2 adsorption-desorption, ESR, and cyclic voltammetry. 3 wt% Cu and 5 wt% Zn were also introduced alternately to MSN (3C-ZM and Z-3CM) to study the metal introduction sequence effect on the properties and catalytic activity. The characterization data showed that an altered arrangement of the silica network was observed with a different structure, particularly in the numbers of Si-O-Si, Si-O-Zn, and Si-O-Cu bonds as well as oxygen vacancies. The catalytic activity regarding the photodecolorization of methyl orange (MO) was in the following order: 3C-ZM > 5C-ZM > Z-3CM > 1C-ZM. The higher numbers of Si-O-Zn, oxygen vacancies, and the higher pore volume of the 3C-ZM catalyst seemeed to be the main factors behind its higher photoactivity compared to the other catalysts. Further optimization by response surface methodology (RSM) with a central composite design (CCD) model was performed for the decolorization of MO. RSM demonstrated that the experimental value (99.89%) was reasonably close to the predicted value (99.99%) with only 0.1% error for MO decolorization at pH 3.5 using 1.6 g L-1 catalyst with 4 wt% Cu loading. (C) 2014 Elsevier B.V. All rights reserved.