Compared　to　homogeneous　catalysis,　heterogeneous　catalysis　allows　for　ready　separation　of　products　from　the　catalyst　and　thus　reuse　of　the　catalyst.　C-C　coupling　is　typically　performed　on　a　molecular　catalyst　which　is　mixed　with　reactants　in　liquid　phase　during　catalysis.　This　homogeneous　mixing　at　a　molecular　level　in　the　same　phase　makes　separation　of　the　molecular　catalyst　extremely　challenging　and　costly.　Here　we　demonstrated　that　a　TiO2-based　nanoparticle　catalyst　anchoring　singly　dispersed　Pd　atoms　(Pd1/TiO2)　is　selective　and　highly　active　for　more　than　10　Sonogashira　C-C　coupling　reactions　(R≡CH　+　R′X　→　R≡R′　X　=　Br,　I;　R′　=　aryl　or　vinyl).　The　coupling　between　iodobenzene　and　phenylacetylene　on　Pd1/TiO2　exhibits　a　turnover　rate　of　51.0　diphenylacetylene　molecules　per　anchored　Pd　atom　per　minute　at　60　°C,　with　a　low　apparent　activation　barrier　of　28.9　kJ/mol　and　no　cost　of　catalyst　separation.　DFT　calculations　suggest　that　the　single　Pd　atom　bonded　to　surface　lattice　oxygen　atoms　of　TiO2　acts　as　a　site　to　dissociatively　chemisorb　iodobenzene　to　generate　an　intermediate　phenyl,　which　then　couples　with　phenylacetylenyl　bound　to　a　surface　oxygen　atom.　This　coupling　of　phenyl　adsorbed　on　Pd1　and　phenylacetylenyl　bound　to　Oad　of　TiO2　forms　the　product　molecule,　diphenylacetylene.　©　2017　American　Chemical　Society.