Density functional theory calculations were used to study the adsorption of NO on Ni-n cluster (n = 1, 2, 3 and 4) doped graphene with different graphene-based support (single vacancy, one nitrogen decorated, two nitrogen decorated and three nitrogen decorated). The adsorption configuration, adsorption energy, charge transfer, density of states of NO on Ni-n/graphene are thoroughly studied. In addition, the d-band center and Fermi softness have been performed to consider the support effect. It is found that the support effect has a significant effect on the adsorption characteristics of NO molecule, which depends on the electronic structure of graphene-based support. The electronic structure can be characterized by the Fermi softness of the catalyst. Ni atom plays a more and more obvious role in NO adsorption process, with the increase of the number of Ni atoms. The Fermi softness is a great descriptors for the adsorption activity of the Ni-n/graphene. This result can contribute to the systematic study of graphene catalysts supported on metal clusters.