Manganese-based catalysts show a tremendous potential in propane oxidation due to their low cost and good catalytic activity but are easily deactivated by SO 2 . In this work, we first synthesized the mesoporous sodium-doped manganese oxide (meso-Na x MnO y ) using the mesoporous silica (KIT-6) as a template after washing with a concentrated NaOH aqueous solution and then prepared the platinum−cobalt bimetallic singleatom (Pt 1 Co 1 /meso-Na x MnO y ) catalyst using the polyvinyl pyrrolidone-protecting one-pot strategy. It was found that the doping of 13.8 wt % Na dramatically enhanced the SO 2 tolerance of meso-Na x MnO y but inhibited its catalytic activity due to the alkali metal poisoning. Among all of the samples for the oxidation of propane, Pt 1 Co 1 /meso-Na x MnO y showed the highest catalytic activity (a propane conversion of 90% was obtained at 282 °C and a space velocity of 30 000 mL g −1 h −1 , and apparent activation energy, specific reaction rate, and turnover frequency at 250 °C were 76.0 kJ mol −1 , 78.9 × 10 −5 mol g Pt −1 h −1 , and 193.7 × 10 −3 s −1 , respectively), which was associated with the Pt and Co double active sites with good dispersion, abundant electron deficiency, outstanding lattice oxygen mobility, good low-temperature reducibility, and large capacity and weak strength of propane adsorption. More importantly, the Pt 1 Co 1 /meso-Na x MnO y sample possessed the excellent resistance to sulfur dioxide. Propane oxidation occurred via different reaction routes over the MnO 2 , meso-Na x MnO y , and Pt 1 Co 1 /meso-Na x MnO y samples, with the Langmuir− Hinshelwood mechanism being dominated. Propane oxidation over Pt 1 Co 1 /meso-Na x MnO y might follow a pathway of propane → acetone and isopropoxide → carboxylate and fatty ether → CO 2 and H 2 O. Pt and/or Co single atoms are highly dispersed on meso-Na x MnO y . SO 2 is preferentially adsorbed at the Na site in Pt 1 Co 1 /meso-Na x MnO y , which protects the active Mn, Pt, and Co from being poisoned by SO 2 , hence making Pt 1 Co 1 /meso-Na x MnO y show good SO 2 resistance in propane oxidation.