Diffusion of single molecules of a substituted terrylene diimide dye in functionalized mesoporous silica films was monitored by single-molecule fluorescence microscopy. By varying the chemical nature and density of the functional groups, the diffusion dynamics of the dye molecules can be controlled precisely. The picture shows a sketch of a dye molecule in a pore, diffusion data for different phenyl functionalization densities, and the trajectory of one molecule in a cyanopropyl-functionalized film. Mesoporous silica materials are promising host structures for diverse applications in nanoscience. Many applications can profit significantly from the ability to influence guest dynamics in the host matrix. To this end, we introduce covalently attached organic functionalization into the walls of mesoporous silica networks. Using single-molecule fluorescence microscopy, we study the diffusion behavior of single terrylene diimide dye molecules in functionalized mesoporous silica films. We show that, through variation of the chemical nature and density of the functional groups, the diffusion dynamics of the dye molecules, in the presence of the surfactant template, can be controlled precisely. The mean diffusion coefficient of the dye molecules increases or decreases depending on the functional group attached to the silica wall. This allows fine-tuning of the diffusion dynamics of the dye by approximately one order of magnitude. The observed changes in the mean diffusion coefficients can be explained by shielding of hydroxyl groups on the silica surface in combination with changes in the rigidity of the micellar packing in the film, as well as direct interactions between the functional groups and the dye molecules.