This paper describes the design and application of V2O5-MoO3/Al2O3 catalysts for the selective oxidation of methanol to dimethoxymethane (DMM). The V2O5-MoO3/Al2O3 catalysts exhibit superior performance for DMM yield than the corresponding samples with V and Mo species only, even at relativity low temperatures. The origin of high DMM yield of the V2O5-MoO3/Al2O3 catalysts is explored and attributed to the synergistic effect of V and Mo mixed oxides presented on the surface of the catalyst. The synergism can be ascribed to (i) the completion of a redox cycle and (ii) the enrichment of weak Bronsted acidic sites. The redox cycle of V-O-Mo oxides could be completed through electron transfer between lattice oxygen and metal cations. The V species exhibits a superior performance in the adsorption and activation of gaseous oxygen, as well as enhanced capability to restore the lattice oxygen and suppress the aggregation of Mo species. The enrichment of weak Bronsted acidic sites is attributed to the addition of MoO3 and the increase of partially reduced V and Mo species, respectively, which is critical to increasing the DMM yield. By adjusting the content of V2O5 and MoO3, we have obtained a 14V(2)O(5)-14MoO(3)/Al2O3 catalyst with the optimized amounts of redox sites and acidic sites, which exhibits a 54% methanol conversion with a DMM selectivity of 92% at 393 K. (C) 2014 Elsevier B.V. All rights reserved.