NiMo catalysts supported on Al-Si supports with 5 wt% Si were prepared by two methods: 1) by incorporating Si into boehmite, followed by drying and calcination producing the catalyst NiMo/Si-Al and 2) by incorporating Si into the surface of an already calcined alumina producing NiMo/Si/Al. These two methods of Si incorporation into the alumina produced different surface structures of the Si oxide overlayer and affected the performance of the supported active Ni-Mo-S phase during the processing of partially hydrotreated Maya crude oil and during cumene hydrocracking, which is used as a model reaction to analyze the acidity function of the catalysts. The purpose of using partially hydrotreated Maya crude oil as feedstock is to test the catalysts in the hydrodesulfurization (HDS) of highly refractory sulfur compounds, such as 4,6-dimethyldibenzothiophene. The supports and catalysts (fresh and spent) are analyzed using nitrogen physisorption, X-ray diffraction, scanning electron microscopy-energy dispersive spectroscopy, and Fourier-transform infrared spectroscopy of surface hydroxyl groups. Depending on the method employed to incorporate Si into the support, the catalyst properties are affected, resulting in higher conversion in hydrotreating (HDT) reactions. The catalysts with Si incorporated into boehmite display the highest activity in the HDT of refractory compounds present in Maya HDT/Diesel HDS (50/50 vol%) feedstock, which is the result of higher dispersion of the active phase, combined with adequate porosity and acidity.