KIT-6 silica with well-ordered three−dimensional (3D) mesopores has been synthesized as a support for nickel-based catalysts. Transmission Electron Microscopy (TEM) and low-angle X-ray Diffraction (XRD) analysis are used to ensure that the ordered 3D mesostructure is stable after NiO incorporation. In this study, the catalytic activities of the NiO/KIT-6 samples are investigated. Additionally, the results show that a 10 wt% NiO/KIT-6 catalyst exhibits high catalytic performance in methane combustion, with T10, T50 and T90 being only 386 °C, 456 °C and 507 °C, respectively. Hydrogen Temperature Programmed Reduction (H2-TPR) studies have shown that the interaction between NiO and KIT-6 in the 10 wt% NiO/KIT-6 catalyst is weak. Methane Temperature programmed Surface Reaction (CH4-TPSR) results show that the surface oxygen of the NiO/KIT-6 catalyst allows it to exhibit a high catalytic performance. NiO/KIT-6 catalysts exhibit superior activities to SBA-15, MCF and SiO2 support catalysts because KIT-6 has a higher surface area and ordered 3D mesopore connectivity, which is favorable for better NiO dispersion and peculiar diffusion for reactant and products. Furthermore, the used catalyst maintained an ordered mesostructure and reduction property.