NiMo/SiO2-Al2O3 mixed oxide supported catalysts were investigated for hydroprocessing of heavy crude oil at moderate reaction conditions. Hydrodesulfurization (HDS), hydrodemetalization (HDM), hydrodeasphaltenization (HDAs) and hydrodenitrogenation (HDN) reactions were studied as function of time-on-stream (TOS). The results indicated that HDS of crude oil corresponds to the number of active metal sites (sulfide phases) present in the catalyst, HDN is enhanced when the catalyst presents a combination of well dispersed sulfide phases and weak to moderate acidity. HDM presented a complex behavior indicating that it is affected significantly not only by the dispersion of the sulfide phase but also by the porosity and acidity of the catalyst. As expected, for HDAs both acidity and textural properties are important. The stability of the catalyst with time-on-stream was affected by coke and metals deposition. The supports and fresh catalysts were characterized by nitrogen physisorption, SEM-EDX, and FT-IR of CO and pyridine adsorption. The results confirm that NiMo/SiO2-Al2O3 catalysts are a good option for the hydrotreatment of heavy oils and that the method used here for support preparation can tune the formation of meso- or macro-porosity and the type and strength of the catalyst acid sites. (C) 2012 Elsevier B.V. All rights reserved.