CO methanation reaction over the Ni/Al 2O 3 catalysts for synthetic natural gas production was systematically investigated by tuning a number of parameters, including using different commercial Al 2O 3 supports and varying NiO and MgO loading, calcination temperature, space velocity, H 2/CO ratio, reaction pressure, and time, respectively. The catalytic performance was greatly influenced by the above-mentioned parameters. Briefly, a large surface area of the Al 2O 3 support, a moderate interaction between Ni and the support Al 2O 3, a proper Ni content (20 wt %), and a relatively low calcination temperature (400 °C) promoted the formation of small NiO particles and reducible β-type NiO species, which led to high catalytic activities and strong resistance to the carbon deposition, while addition of a small amount of MgO (2 wt %) could improve the catalyst stability by reducing the carbon deposition; other optimized conditions that enhanced the catalytic performance included high reaction pressure (3.0 MPa), high H 2/CO ratio (>3:1), low space velocity, and addition of quartz sand as the diluting agent in catalyst bed. The best catalyst combination was 20-40 wt % of NiO supported on a commercial Al 2O 3 (S 4) with addition of 2-4 wt % of MgO, calcined at 400-500 °C and run at a reaction pressure of 3.0 MPa. On this catalyst, 100% of CO conversion could be achieved within a wide range of reaction temperature (300-550 °C), and the CH 4 selectivity increased with increasing temperature and reached 96.5% at a relatively low temperature of 350 °C. These results will be very helpful to develop highly efficient Ni-based catalysts for the methanation reaction, to optimize the reaction process, and to better understand the above reaction.