The　activation　and　hydrogenation　of　CO2　at　the　Cu/TiO2　interfaces　that　are　formed　by　depositing　subnanometer　Cu-n　(n　=　1-8)　clusters　on　TiO2(110)　surfaces　have　been　systematically　investigated　using　density　functional　theory　calculations.　The　most　stable　structures　with　a　bent　CO2　delta-　configuration　at　the　Cu-n/TiO2　interfaces　are　determined,　which　indicate　that　the　binding　strength　of　CO2　on　the　Cu-n/TiO2　(110)　surface　can　be　tuned　by　controlling　the　size　of　the　deposited　Cu　cluster.　It　is　interesting　that　the　copper　cluster　with　a　specific　size　of　Cu-4　exhibits　a　distinct　preference　for　CO2　activation,　and　the　strongest　binding　interaction　between　CO2　and　Cu-4/TiO2　(110)　is　mainly　ascribed　to　the　formation　of　the　strong　Cu-C　and　Ti-O　adsorption　bonds.　The　reaction　mechanisms　of　CO2　conversion　to　CH3OH　at　the　Cu-4/TiO2　(110)　interface　via　the　formate　and　the　reverse　water　gas　shift　(RWGS)　+　CO-hydrogenation　pathways　are　further　investigated　by　microkinetic　simulations.　The　production　of　CH3OH　over　Cu-4/TiO2　is　mainly　via　the　RWGS　pathway　to　yield　CO　followed　by　the　formation　of　H3CO*　as　the　most　stable　intermediate,　while　the　formate　pathway　is　not　efficient　enough　because　of　the　higher　apparent　activation　energy　of　CH3OH　generation　and　the　overly　strong　binding　of　HCOO*　species　at　the　interface.　Compared　with　other　Cu-n/TiO,　interfaces,　the　TiO2　(110)　surface-supported　size-selected　Cu(4　)cluster　exhibits　the　highest　CO2　hydrogenation　activity.　The　findings　obtained　in　the　present　work　provide　useful　insight　to　design　Cu/oxide　interfaces　with　high　activity　toward　methanol　synthesis　from　CO2　hydrogenation　by　precisely　controlling　the　size　of　copper　clusters.