Understanding　metal-support　interactions　is　critical　to　the　rational　design　of　a　catalyst　for　CO2methanation.　In　this　regard,　the　density　functional　theory　is　employed　to　shed　light　on　the　factors　that　determine　the　difference　between　RuTiO2-　and　TiO2-supported　Ru　nanoparticles.　Structural　observations　and　the　calculated　ratio　of　cohesive　energy　and　adsorption　energy　(Ecoh/Eads)　suggest　that　supported　Ru6could　form　as　an　epitaxial　layer　along　with　RuTiO2as　well　as　display　strong　metal-support　interactions　with　TiO2and　thereby　is　used　as　a　surface　model　to　simulate　the　nanoparticles　employed　in　the　experiment.　Furthermore,　electronic　analysis　reveals　that　due　to　the　existence　of　a　RuO2overlayer,　more　electrons　are　transferred　from　the　support　to　the　Ru　cluster.　Benefiting　from　this,　CO2is　lower　in　adsorption　energy　since　electrons　from　Ru6/RuTiO2are　less　likely　to　fill　in　the　antibonding　orbital　of　Ru-O　interaction.　Analysis　of　the　minimum-energy　pathway　indicates　that　the　methanation　of　CO2is　led　by　C-O　direct　bond　cleavage　rather　than　the　formate　pathway　in　the　first　place　for　both　surfaces,　which　is　consistent　with　the　FTIR　spectroscopy　results.　Besides,　we　noticed　that　different　reaction　mechanisms　control　methane　synthesis　from　the　onset　of　CHO∗　formation.　On　the　one　hand,　CHO∗　prefers　an　associative　mechanism　on　Ru6/RuTiO2due　to　the　lower　d-band　center　of　the　support　and　facile　formation　of　CH2O∗　species.　On　the　other　hand,　closer　proximity　of　the　d-band　center　to　the　Fermi　level　(EFermi)　and　preferable　CH∗　formation　promote　CHO∗　on　Ru6/TiO2to　undergo　a　dissociative　pathway.　Our　comparative　studies　suggest　that　the　RuO2overlayer　plays　a　key　role　in　determining　the　reaction　mechanism　of　CO2methanation　for　Ru/r-TiO2,.　©　2022　American　Chemical　Society.　All　rights　reserved.