The interface of metal-oxide plays pivotal roles in catalytic reactions, but its catalytic function is still not clear. In this study, we report the high activity of nanostructured Ru/ceria (Ru-clusters/ceria) in the ethylene methoxycarbonylation (EMC) reaction in the absence of acid promoter. The catalyst offers 92% yield of MP with TOF of 8666 h(-1), which is about 2.5 times of homogeneous Pd catalyst (similar to 3500 h(-1)). The interfacial Lewis acid base pair [Ru-O-Ce-Vo], which consists of acidic Ce-Vo (oxygen vacancy) site and basic interfacial oxygen of Ru-O-Ce linkage, acts as active site for the dissociation of methanol and the subsequent transfer of hydrogen to the activated ethylene, which is the key step in acid-promoter-free EMC reaction. The combination of H-1 MAS NMR, pyridine-IR and DFT calculations reveals the hydrogen species derived from methanol contains Bronsted acidity. The EMC reaction mechanism under acid-promoter-free condition over Ru-clusters/ceria catalyst is discussed.