The coupling relationship of fluidization behavior, reaction activity and particle structure of Ni/MgO catalyst toward fluidized CO methanation is systematically investigated. The poor fluidization quality or defluidization, to a large extent, is caused by the rapid decrease in gas volume induced by methanation reaction. This reaction derived defluidization or poor fluidization results in great changes in structure and chemical compositions of the Ni/MgO catalyst, and which in turn lead to a decrease of reaction activity. The better fluidization quality catalyst is beneficial for maintaining the catalyst structure and exhibits the higher resistance to the negative effect by rapid decrease of the gas volume. The fluidization quality of the stable fluidized catalyst can be improved by addition of N-2. However, the catalyst particles with poor fluidization quality are easy to be defluidized due to the rapidly decrease in gas volume even with addition of inert components.