To prepare the highly active hydrodesulfurization (HDS) catalyst, modified Zr-KIT-5 materials were synthesized by in situ synthesis method and supported NiMoW trimetallic active phases for dibenzothiophene (DBT) and 4,6-dimethyldibenzothiphene (4,6-DMDBT) hydrodesulfurization reactions. The analysis of Fourier-transform infrared and X-ray photoelectron spectroscopy proved that Zr species had been incorporated into the skeleton of mesoporous KIT-5 material. Moreover, it was demonstrated from the Py-IR and high-resolution transmission electron microscopy characterizations that the embedded Zr species not only enhanced the acidity of catalysts but also modulated the distribution of active metals. Among all of the modified trimetallic catalysts, the NiMoW/ZrKT-60 displayed the highest HDS activities of DBT (99.5%) and 4,6-DMDBT (91.0%), which was derived from the open and large three-dimensional mesoporous channel, suitable acidity, and appropriate Mo(W)S-2 dispersion. Furthermore, for 4,6-DMDBT reaction, the NiMoW/ZrKT-60 catalyst with the highest B/L ratio (0.22) showed higher hydrogenation and the highest isomerization selectivity.