Using renewable H2 for CO2 hydrogenation to methane not only achieves CO2 utilization, but also mitigates the greenhouse effect. In this work, several Ni-based catalysts with V species using 3D-mesoporous KIT-6 (Korea Advanced Institute of Science and Technology, KIT) as support were prepared at different contents of NiO and V2O5. Small Ni nanoparticles with high dispersibility on 20Ni-0.5V/KIT-6 were identified by X-ray diffraction (XRD), TEM and hydrogen temperature-programmed desorption (H2-TPD) analysis, which promoted the production of more Ni active sites for enhancing catalytic activity for CO2 methanation. Moreover, TEM and hydrogen temperature-programmed reduction (H2-TPR) characterizations confirmed that a proper amount of Ni and V species was favorable to preserve the 3D-mesoporous structure and strengthen the interaction between active Ni and KIT-6. The synergistic effect between Ni and V could strengthen surface basicity to elevate the ability of CO2 activity on the 20Ni-0.5V/KIT-6. In addition, a strong interaction with the 3D-mesoporous structure allowed active Ni to be firmly anchored onto the catalyst surface, which was accountable for improving catalytic activity and stability. These results revealed that 20Ni-0.5V/KIT-6 was a catalyst with superior catalytic activity and stability, which was considered as a promising candidate for CO2 hydrogenation to methane.