Two series of supported nanoscaled NiO catalysts have been prepared using Nb2O5 supports with different surface areas. NiO nanoparticles interacting with Ni-O-Nb mixed phases are active and selective for ethane ammoxidation; both are required in order to have an active and selective catalyst. In this paper we report the dispersion of NiO nanoparticles on two Nb2O5 supports in order to generate an active phase for ethane ammoxidation. The use of a support stabilizes NiO nanoparticles, which otherwise would sinter. This work shows how the activity can be modulated by the size of the NiO nanoparticles and by the NiO/Ni-Nb-O ratio, which depends on the nickel coverage and support surface area. The catalysts obtained are very promising for ethane ammoxidation reaction.