Highly dispersed Ni catalyst and alkaline promoters supported by mesoporous SiO₂ nanospheres were synthesized and applied as an active and stable catalyst for dry reforming of methane (DRM). The as-prepared Ni/MgO-mSiO₂ catalyst showed stable conversions of CH₄ and CO₂ around 82% and 85% in 120 h of DRM reaction, which was superior in performance compared to similar catalysts in literatures. Based on the transmission electron microscope (TEM) images, energy-dispersive spectroscopy (EDS), CO-pulse adsorption, temperature programmed reduction of the oxidized catalysts by hydrogen (H₂-TPR), X-ray photoelectron spectroscopy (XPS), temperature-programmed desorption of CO₂ (CO₂-TPD), and thermal gravitational analysis (TGA), the promotion effect of MgO on the Ni catalyst was systematically studied. The introduction of Mg²⁺ in synthesis enhanced the interaction between Ni²⁺ and mSiO₂, which led to a high dispersion of active centers and a strong “metal–support” interactions to inhibit the sintering and deactivation of Ni at reaction temperatures. On the other hand, Ni and MgO nanoparticles formed adjacently on mSiO₂, where the “Ni-MgO” interface not only improved the Ni⁰ distribution and promoted the cracking of CH₄ but also promoted the activation of CO₂ and the elimination of carbon deposits. A high and stable conversion of CH₄ and CO₂ were then achieved through the synergistic effect of Ni catalyst, MgO promoter, and mSiO₂ support.