Using a chemical reaction dynamics software of CHEMKIN and the CFD software, the influences of T, W/C, O/C and catalysts activity density on methane conversion, carbon deposition and the yields of H2, CO and CO2 are investigated in the reaction of autothermal reforming of methane in a micro-reactor. The results show that optimum conditions of methane autothermal reforming are the oxygen–carbon ratio of 0.4, the water-carbon ratio of 2.1, the temperature of 1073 K, the flow velocity of 1 m/s and the catalyst active site density of 9.98 × 10−6 kmol/m2. Under these conditions, the methane conversion rate, the yields of H2 and CO are 93–99%, 65–80% and 50–65%, respectively. The total carbon deposition is about 1.65 × 10−12 kmol/m2. Moreover, the investigation and development of the three-dimensional spiral multi-cylinder micro-reactor are essential for applications of the mobile fuel cell in the Micro-Electro-Mechanical Systems (MEMS) field.