Organosilicon monoliths carrying chromatographic ligands with different alkyl chain lengths were obtained by thiol-methacrylate photopolymerization. The use of thiol-ene chemistry in the presence of a main monomer with a series of methacrylate functionality (i.e., methacrylate substituted polyhedral oligomeric silsesquioxane) allowed the synthesis of organosilicon monoliths with high cross-linking density and carrying hydrophobic alkyl-chain ligands by a one-pot process. In the synthesis runs, 1-butanethiol, 1-octanethiol, and 1-octadecanethiol were used as the hydrophobic thiol ligands with the number of methylene units between 4 and 18. The selectivity analysis performed using cytosine/uracil retention ratio showed that alkanethiol-attached organosilicon monoliths exhibited hydrophobicity close to octadecyl-attached silica-based RP columns. In the RP, chromatographic runs performed in nano-liquid chromatography, phenols, alkylbenzenes, and PAHs were used as the analytes. Among the synthesized monoliths, retention-independent plate height behavior and the smallest plate heights were obtained with 1-octadecanethiol-attached organosilicon monolith for the analytes in a wide polarity range. With this monolith, the mobile phases prepared with ACN contents ranging between 35 and 85% v/v could be used for satisfactory separation of analytes in a wide polarity range.