Serial Al-Ti-SBA-16 materials with highly ordered degree were successfully synthesized by a simple two-step method. The characterization results showed that incorporation of Al and Ti atoms into SBA-16 silica could obtain the supports with different acidities and modulate the distribution and dispersion of active phases for NiMo catalysts. The dibenzothiophene (DBT) hydrodesulfurization (HDS) evaluation results disclosed that the synergistic effect of enhancing acidity and properties of active metals could significantly improve the HDS performance. Importantly, it was the first time that the ratios of S-edge and Mo-edge concentrations were found to be well linked with the hydrogenation pathway (HYD)/direct desulfurization pathway (DDS) ratios. The HDS result showed that the acidity of S-H groups in S-edge sites could be promoted by B acid and further facilitated the DDS selectivity. As the Al and Ti contents in the support were 7.5% and 2.5% respectively, the NiMo/AT-7.5 catalyst exhibited the highest HDS performance due to its appropriate acidity, highest proportion of MoS2 phase and concentration of S-edge sites with high efficiency. Finally, the kinetic and thermodynamic analyses were applied to investigate the intrinsic HDS reactivity for various catalysts. The results confirmed the existence of synergistic effect in the DBT HDS reaction. It was also discovered that the B acid sites could further increase the desulfurization route (DS) of THDBT to CHB. In addition, the S-edge/Mo-edge ratio and kDDS/kHYD could also be well linked.