Methyl glycolate (MG) is an important building block for synthesizing biodegradable material of polyglycolic acid. Hydrogenation of coal-based dimethyl oxalate (DMO) to MG is quite promising, where Ag-based catalysts exhibited excellent selectivity. Here, a series of Ag/SiO2-x catalysts with particle sizes of 1.4–13.5 nm were prepared, which showed significant structural sensitivity in DMO hydrogenation. For Ag nanoparticles of 1.4–2.7 nm, the turnover frequency (TOF) was linearly increased with the surface electron density of silver, but when the Ag nanoparticles further enlarged, no significant variation of TOF was observed. Combining DFT calculation and experimental results of the model catalyst, triangular nanoplate, it was deduced that the Ag (111) played a dominant role in DMO hydrogenation to MG, originating from the benefited MG desorption as well as promoted dissociation of H2 and DMO. This understanding about Ag particle size effect may provide guidance for designing efficient catalysts for DMO hydrogenation to MG.