Highly selective production of CH4 from photocatalytic CO2 reduction is still a great challenge which involves the kinetically unfavorable transfers of 8 protons and 8 electrons. Herein, CeO2 photocatalysts incorporated with isolated Ru single-atoms have been fabricated, which demonstrate dramatically elevated selectivity of CH4 from CO2 reduction. The introduced Ru single-atoms promote carrier separation and accelerate electron transfer, which efficiently enhances the photocatalytic activity. Density functional theory (DFT) calculations and in situ FT-IR analysis manifest that the Ru single-atom active sites play an indispensable role in strengthening the adsorption of *CO intermediate on the catalyst surface and promoting H2O oxidation to generate abundant protons, thus favoring *CO protonation into *CHxO (x = 1, 2, 3) species and final deoxygenation into CH4. This work provides an effective strategy by constructing single-atom active sites to modulate and stabilize the key intermediates of CO2 photoreduction to improve the selectivity of the target products.