Recently, the Cu-based catalyst has attracted wide attention for the hydrogenation of dimethyl oxalate (DMO) to ethylene glycol (EG) due to its high catalytic activity and it is low cost. However, its poor stability, ease of agglomeration, and the short life of the catalyst restrict its further development in industrial applications. Here, we constructed a novel MOF-derived Cu/SiO2 catalyst (MOF-CmS for short) with a controllable distribution of Cu active sites for the hydrogenation of the DMO to EG reaction. The catalyst was prepared by a hydrothermal method with the HKUST-1 uniformly coated on the surface of the silica microspheres. After the calcination, the highly dispersed and uniform Cu species were loaded on the surface of the silica. The resulted MOF-CmS catalyst showed a 100% conversion of DMO and over 98% selectivity of EG at 200 °C and 2 MPa while a traditional Cu/SiO2 catalyst exhibited serious agglomeration of Cu active sites and low catalytic activity (DMO conversion of 86.9% and EG selectivity of 46.6%). It is believed that the highly dispersed active metal center and the interaction between the active metal and carrier were the main reasons for higher catalytic activity of the MOF-CmS catalyst. Therefore, the developed method opened another avenue to synthesize highly dispersed and stable Cu-based catalysts.