Herein, a series of mesoporous NiMo/LaAlOx with various La contents were constructed through a solvent evaporation-induced self-assembly protocol, and their catalytic activities were investigated for hydrodesulfurization (HDS) of 4,6-DMDBT. It has been confirmed that the incorporation of La influences the electronic structure and morphology of NiMoS active phase. The lower amount of La (x ≤ 1.0 wt.%) could facilitate the formation of “Type II” NiMoS phase by weakening the interaction of Mo-O-Al leakage and promoting the sulfidation of both Mo and Ni species as well as increasing the ratio of “Type II” NiMoS phase, thereafter boosting the HDS performances. Further increasing La incorporation, however, leads to the generation of inactive NiSx phase and decrease of NiMoS active phase proportion, the HDS activities of corresponding catalysts were suppressed. NiMo/LaAlOx-1.0 exhibits the highest activity for 4,6-DMDBT HDS because of its moderate metal-support interaction, optimal morphology and the largest proportion of “Type II” NiMoS active phase.