Highly ordered mesoporous silica with Pm3n cubic mesostructure and cube-like morphology was facilely fabricated in a cost-efficient aqueous-phase synthesis system. The obtained cubic mesoporous silica (CMS) modified with various aluminum contents were taken as supports to prepare NiMo/Al-CMS catalysts, and the corresponding hydrodesulfurization performance of dibenzothiophene was subsequently assessed. The results showed that as-prepared CMS exhibited a large surface area (865 m2/g) and pore volume (0.92 cm3/g). The incorporated aluminum brought many advantages such as enhanced acidity, modulated metal–support interaction, and improved active metals dispersity, all of which contributed to the high sulfidation degree of catalysts. As a result, the NiMo/Al-CMS-10 catalyst presented superior HDS activity and a higher selectivity for the direct desulfurization route, deriving from a synergistic effect of its admirable textural characteristics, increased acidic property, highly sulfided active phases, and well-dispersed MoS2 slabs with moderate stacking layer and slab length.