Pre-treated silica with a plasma-deposited (PD) layer of polymerized precursors was tested concerning its compatibility with Natural Rubber (NR) and its influence on the processing of silica-silane compounds. The modification was performed in a tailor-made plasma reactor. The degree of deposition of the plasma-coated samples was analyzed by ThermoGravimetric Analysis (TGA). In addition, Diffuse Reflectance Infrared Fourier Transform spectroscopy (DRIFTs), X-ray Photoelectron Spectroscopy (XPS), and Transmission Electron Microscopy (TEM) were performed to identify the morphology of the deposited plasma polymer layer on the silica surface. PD silica samples were incorporated into a NR/silica model compound. NR compounds containing untreated silica and in-situ silane-modified silica were taken as references. The silane coupling agent used for the reference compounds was bis-(3-triethoxysilyl-propyl)disulfide (TESPD), and reference compounds with untreated silica having the full amount and 50% of silane were prepared. In addition, 50% of the silane was added to the PD silica-filled compounds in order to verify the hypothesis that additional silane coupling agents can react with silanol groups stemming from the breakdown of the silica clusters during mixing. The acetylene PD silica with 50% reduced silane-filled compounds presented comparable properties to the in-situ silane-modified reference compound containing 100% TESPD. This facilitates processing as lower amounts of volatile organic compounds, such as ethanol, are generated compared to the conventional silica-silane filler systems.