Deep hydrodesulfurization (HDS) of oil fractions is a key process in petroleum refineries due to theincreasing demand for S-free diesel and gasoline fractions. In this work, a series of NiMo catalysts sup-ported on Al- and P-modified HMS mesoporous substrate were tested in the HDS of thiophene and4,6-dimethyldibenzothiophene (4,6-DMDBT) to evaluate the effect of Al and P additives on the catalystresponse in HDS reactions (thiophene at 1 bar and 4,6-DMDBT at 5.5 MPa). The catalysts were charac-terized by a variety of techniques (XRD, N2adsorption–desorption, TPR, TPS, FT-IR of adsorbed pyridine,UV–vis and H2chemisorption). NiMo/Al-HMS-P catalyst containing 1.0 wt.% of P exhibited the best perfor-mance in both HDS reactions as a consequence of the proper balance between the active phase dispersionand the largest hydrogenation ability among the studied catalysts. The 4,6-DMDBT HDS reaction pro-ceeded toward direct desulfurization (DDS) and hydrogenation (HYD) reaction routes. Concerning theHDS of thiophene, the increase of the catalyst acidity led to the formation of butadiene and diminishedthe hydrogenation of olefins (formation of butane). At the reaction temperature of 320◦C, the NiMo/Al-HMS-P1.0 catalyst exhibited the highest activity and the lowest butane formation among the catalystsstudied. The isomerization of olefins in the thiophene HDS reaction did not occur, in line with the observedabsence of isomerization in the 4,6-DMDBT HDS reaction.