We report here the development of Pd-supported catalysts for the selective C-3 arylation of free-indole using thiol-functionalized silica supports to anchor the palladium centers. The palladium (II) complex, Pd(OAc)2, was efficiently loaded into various thiol-functionalized mesostructured silicas at room temperature. These materials exhibit different contents of surface SH groups (0.3 to 1.8 SH/nm2) and various SH/Pd molar ratios from 6 to 65. It was found that the catalysts containing the most isolated surface SH groups (0.3 SH/nm2) and the highest loading of Pd were the most active, reaching 70% of conversion, 1400 as turnover numbers and 100% selectivity in the C-3 arylated product using only 0.05 mol% of Pd. However, a leaching of active Pd species (1.7 ppm) was detected. The best compromise was found for a specific solid containing isolated surface thiol groups (0.3 SH/nm2) and a very low loading of Pd (SH/Pd = 65). It exhibited a high TON (608) with a very low Pd leaching of 0.5 ppm in the course of the catalytic reaction. These results thus illustrate that both surface SH site isolation and concentration, as well as the SH/Pd ratio are key parameters to access high catalytic performances and very low leaching of metal during catalysis.