A series of ZrO2-Al2O3 (designated as ZA) mixed supports with different ZrO2 contents were prepared by a simple complexing-deposition method using ZrOCl2 8H2O and Al2O3 as starting materials. These samples were characterized by inductively coupled plasma-atomic emission spectroscopy (ICP–AES), X-ray diffraction (XRD), N2 adsorption analysis, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The results demonstrated that zirconia nanoparticles with a size of about 5 nm in amorphous phase were well dispersed on alumina. The sulfided CoMo catalysts supported on the mixed supports showed a higher dibenzothiophene (DBT) hydrodesulfurization (HDS) activity than those supported on alumina and a commercial HDS catalyst KF757. The NO adsorption analysis revealed that the CoMo/ZA catalysts provided more active sites when the support contained a suitable ZrO2 content. Further, it was found, by high-resolution transmission electron microscopy (HRTEM), that the addition of ZrO2 had an obvious effect on the sulfide component’s morphology: a multi-layered structure of CoMoS was formed on ZA supports while a mono-layered structure was formed on Al2O3. The multi-layered CoMoS on the mixed supports provided more active sites and higher activity for HDS of DBT due to a less steric hindrance.