Stability　and　reactivity　of　single-atom　catalysts　(SACs)　are　the　points　of　concern　in　catalysis,　especially　under　the　harsh　conditions,　such　as　at　elevated　temperatures　in　oxidizing　conditions.　Previous　work　showed　that　thermally　stable　Pt1　SAC　supported　on　K-modified　MgAl2O4　prepared　by　a　vapor-phase　self-assembly　mechanism　(Pt1/K/MgAl2O4)　showed　better　performance　than　a　Pt/MgAl2O4　nanocatalyst　in　catalytic　CH4　oxidation　(Chem,　2022,　8,　731–748).　However,　the　detailed　reaction　mechanism　remains　unclear,　which　preventing　the　further　development　of　single-atom　catalysts　for　CH4　oxidation.　Herein,　the　sintering　resistance　behaviour　of　the　Pt1/K/MgAl2O4　catalyst,　was　investigated　by　means　of　density　functional　theory　(DFT)　calculations,　and　it　was　found　that　the　catalytic　CH4　oxidation　takes　place　via　the　Mars-van　Krevelen　(MvK)　mechanism,　similar　to　that　on　conventional　oxides.　This　viewpoint　is　further　verified　by　experiments.　Additionally,　other　noble　metals　(Au,　Ir　and　Ru)　and　alkali　elements　(Na　and　Cs)　are　also　investigated　and　it　is　found　that　the　alkali　types　also　affect　the　catalytic　performance.　This　work　clarifies　the　reaction　mechanism　of　CH4　oxidation　on　metal　SAC　supported　on　MgAl2O4　synthesized　at　high　temperature,　providing　a　chance　to　manipulate　the　performances　of　metal　SAC　in　CH4　oxidation.　©　2022　Wiley-VCH　GmbH.