Rutile TiO2 supported single atom Au catalyst for promoting methanol dehydrogenation activity in direct methanol fuel cell (DMFC) has been investigated by using density functional theory calculations. Rutile Au1/TiO2 (110) and non-doped rutile TiO2 (110) surfaces are conducted due to their lowest index and energy. Fruitfully, rutile Au1/TiO2 (110) surface exhibits the excellent catalytic performance on methanol dehydrogenation, being prone to reform under alkali conditions; its lattice gold, titanium and oxygen atoms are involved in the whole methanol dehydrogenation process, along with the intermediate adsorbates. Methanol, via the activation of OH and C–H bonds on rutile Au1/TiO2 (110) surface, proceeds the subsequent stripping of the possible intermediate products: H2, HCHO, CO and CO2 to gas phase separately. Despite the most difficult step among them, CO2 stripping benefits considerably from the unique rutile TiO2 (110) surface and alkali participation.