Nickel-based catalyst is widely used in CO methanation reaction owing to its high activity and selectivity. However, the catalyst is very prone to sulfur poisoning, leading to deactivation. It is urgent to develop nickel-based catalyst with high efficiency, stability, and good resistance. It is well known that different preparation methods have obvious influence on physicochemical and textural properties of the catalyst. In this paper, nickel-based catalyst with NiO content of 20% was prepared by wet impregnation and co-precipitation methods separately. The catalysts were characterized by means of H2 chemical adsorption, BET, XRD, H2-TPR, Raman Spectrometry, and XPS. The activity and sulfur resistance of the catalyst for CO methanation reaction were systematically evaluated in a fixed bed microreactor. The results show that the 20 Ni-Al2O3 catalyst prepared by precipitation method exibited better activity and sulfur resistance than that prepared by impregnation(20 Ni/Al2O3). Under the conditions of t=240 ℃, p=0.1 MPa, and WHSV=20 000 mL·g-1·h-1, the CO conversion rate over 20 Ni-Al2O3 catalyst was 99%, and the yield of CH4 was above 97%. CO conversion rate and the yield of CH4 were 75% and 61% when the accumulative amount of H2S pulse injection was 1.5 mL. The excellent activity and sulfur resistance of 20 Ni-Al2O3 catalyst are due to the large specific surface area of Ni on catalyst surface generating more active sites, leading to its high low temperature activity. The increase of H2S adsorption capacity may effectively delay sulfur poisoning and improve sulfur resistance.