New catalysts for deep hydrodesulfurization (HDS) of diesel oil were prepared by loading the active metal components on the TiO2-SiO2 composite supports, which were synthesized by a sol-gel and supercritical fluid drying method. The HDS performance of the prepared catalysts for RFCC (resid fluid catalytic cracking) diesel oils was evaluated in a fixed-bed reactor under different conditions. The major sulfur compounds in the RFCC diesel oils are alkyl substituent benzothiophenes (BTs), dibenzothiophene (DBT), and alkyl substituent dibenzothiophenes (DBTs), in which the alkyl DBTs with alkyl groups at the 4 and/or 6 positions, such as 4,6-DMDBT and 4-MDBT, are the refractory compounds. The effects of the catalyst properties on the HDS performance for different sulfur compounds, especially the refractory compounds, in the diesel oils were studied. It was found that the catalysts supported on TiO2-SiO2 composites with higher ratios of Lewis acid sites and with Ni-W active components presented better HDS performance for the alkyl DBTs. The HDS performance of the catalysts for removing of alkyl DBTs can be further improved through increasing the concentration and intensity of Lewis acid by adding F and P into the catalysts.