In this study, the liquid phase and vapor phase procedures for silylating cellulose microfibers by hexamethyldisilazane (HMDS) were compared in terms of efficiency. The influence of functionalization degree on the morphology of microfibers and their interaction with polydimethylsiloxane (PDMS) matrix has been investigated. The antibacterial properties of silylated cellulose microfibers hybridized with Ag nanoparticles, obtained by in situ chemical reduction, were also studied. Sample morphology investigations were carried out using spectroscopy and microscopy techniques (FTIR, XPS, TEM, SEM, EDS, XPS). Trimethylsilyl moieties appear on the surface of the cellulose microfibers after modification and improve the dispersibility of the microfibers, allowing strong interaction with the PDMS matrix and favoring its crosslinking density. Microfibers functionalized by the vapor phase of HMDS show smoother surfaces with higher concentrations of Si-containing groups, resulting in a more hydrophobic wetting behavior and a greater influence on the mechanical properties of the polymer. The silylated cellulose microfiber–Ag nanohybrid shows stronger antimicrobial activity towards Gram-positive and Gram-negative bacteria strains compared to that of the untreated hybrid. A PDMS composite loaded with this hybrid exhibits the ability to inhibit bacterial growth.