Since　the　discovery　that　ceria　is　an　active　catalyst　for　selective　hydrogenation　of　alkynes,　there　has　been　much　debate　on　the　catalytic　mechanism.　In　this　work,　we　propose,　based　on　density　functional　theory　(DFT)　investigations,　a　mechanism　that　involves　the　heterolytic　dissociation　of　H2　at　oxygen　vacancies　of　CeO2(111),　facilitated　by　frustrated　Lewis　pairs　consisting　of　spatially　separated　O　and　Ce　sites.　The　resulting　O-H　and　Ce-H　species　effectively　catalyze　the　hydrogenation　of　acetylene,　avoiding　the　overstabilization　of　the　C2H3∗　intermediate　in　a　previously　proposed　mechanism.　On　the　basis　of　our　mechanism,　we　propose　the　doping　of　ceria　by　Ni　as　a　means　to　create　oxygen　vacancies.　Interestingly,　the　Ni　dopant　is　not　directly　involved　in　the　catalytic　reaction,　but　serves　as　a　single-atom　promoter.　Experimental　studies　confirm　the　design　principles　and　demonstrate　much　higher　activity　for　Ni-doped　ceria　in　selective　hydrogenation　of　acetylene.　The　combined　results　from　DFT　calculations　and　experiment　provide　a　basis　to　further　develop　selective　hydrogenation　catalysts　based　on　earth-abundant　materials.　©　2018　American　Chemical　Society.