Direct　selective　oxidation　of　methane　(DSOM)　to　high　value-added　oxygenates　under　mild　conditions　is　attracting　considerable　interest.　Although　state-of-the-art　supported　metal　catalysts　can　improve　methane　conversion,　it　is　still　challenging　to　avoid　the　deep　oxidation　of　oxygenates.　Here,　we　develop　a　highly　efficient　metal-organic　frameworks　(MOFs)-supported　single-atom　Ru　catalyst　(Ru1/UiO-66)　for　the　DSOM　reaction　using　H2O2　as　an　oxidant.　It　endows　nearly　100%　selectivity　and　an　excellent　turnover　frequency　of　185.4　h-1　for　the　production　of　oxygenates.　The　yield　of　oxygenates　is　an　order　of　magnitude　higher　than　that　on　UiO-66　alone　and　several　times　higher　than　that　on　supported　Ru　nanoparticles　or　other　conventional　Ru1　catalysts,　which　show　severe　CO2　formation.　Detailed　characterizations　and　density　functional　theory　calculations　reveal　a　synergistic　effect　between　the　electron-deficient　Ru1　site　and　the　electron-rich　Zr-oxo　nodes　of　UiO-66　on　Ru1/UiO-66.　The　Ru1　site　is　responsible　for　the　activation　of　CH4　via　the　resulting　Ru1═O*　species,　while　the　Zr-oxo　nodes　undertake　the　formation　of　oxygenic　radical　species　to　produce　oxygenates.　In　particular,　the　Zr-oxo　nodes　retrofitted　by　Ru1　can　prune　the　excess　H2O2　to　inactive　O2　more　than　•OH　species,　helping　to　suppress　the　over-oxidation　of　oxygenates.　©　2023　American　Chemical　Society.