Cu-CeO2 systems are widely used in solid oxide fuel cells and water gas shift reaction because of its special catalytic ability. The interfacial properties of the Cu/CeO2 (110) with the adsorption of Cu atom and Cu cluster are investigated in terms of first-principles based on density functional theory. It is found that: 1) the single Cu adatom prefers to be adsorbed on the oxygen bridge site; 2) the adsorbed tetrahedron structure of Cu4 cluster is the most stable cluster configuration on CeO2(110) surface; 3) the metal-introduced gap states in the gap area are mainly from the adsorbed Cu (cluster), its neighboring oxygcr and the reduced cerium ion(s), indicating that the activity of CeO2(110) surface is improved by copper adsorption; 4) the adsorbed Cu adatom and Cu4 cluster are oxidized to Cuδ+ and Cu4δ+ by their neighboring Ce ion(s) with the formation of Ce3+ ion(s), the reaction could be summarized as Cux/Ce4+→ Cuxδ+/Ce3+; 5) the adsorption of small clusters introduces more Ce3+ ions than a single Cu atom does, indicating that more Cuδ+-Ce3+ catalytic active centers are formed. The current study on Cu/CeO2(110) together with our previous results on Cu/CeO2(111) presents a good understanding of the synergies between Cu and ceria, and reveals the improvement of the activity of ceria by Cu adsorption.