Gas-phase hydrogenation of dimethyl oxalate (DMO) on a copper-based catalyst is one of the crucial technologies in the production of ethylene glycol (EG) from syngas. Even though Cu/SiO2 catalyst is widely used in ester hydrogenation reactions, a kinetics study considering multiple active sites has not yet been reported. In this study, a series of experiments were carried out to investigate the heterogeneous catalytic reaction kinetics of the hydrogenation of DMO over Cu/SiO2 catalyst. Considering different situations of ester adsorption, H-2 adsorption, and active sites, 34 possible kinetics models were proposed and screened to identify the one most appropriate to describe the hydrogenation of DMO over Cu/SiO2 catalyst. With the help of relevant thermodynamic theories and statistical evaluations, the optimal model was found to fit well to our experimental data. This model proved that the hydrogenation of DMO depends on the synergistic effect of two active sites, wherein hydrogen and the ester were adsorbed on two different active sites with dissociative states. The dissociative adsorption of the ester was found to be the rate-controlling step in the hydrogenation of DMO over Cu/SiO2 catalyst prepared by an ammonia-evaporation method.