This work examines the antifouling effect of quaternary ammonium silane (QAS) grafted from coatings of silica nanoparticles (SiNPs), independently and in combination with a zwitterionic sulfobetaine (SB) silane. The binding of QAS to the SiNP coatings was monitored using quartz crystal microgravimetry with dissipation monitoring (QCM-D) under varied pH and solution concentrations. Adsorption of bovine serum albumin protein was reduced on QAS modified SiNP coatings prepared under alkaline conditions due to the proposed generation of a pseudozwitterionic interface, where the underlying SiNP surface presents an anionic charge at high pH. Significant reductions in protein binding were achieved at low functionalization concentrations and short modification times. Additionally, SiNP coatings modified with a combination of QAS and SB chemistries were investigated. Surface modifications were performed sequentially, varying silane concentration and order of addition, and monitored using QCM-D. Dual-functionalized surfaces presented enhanced resistance to protein adsorption compared to QAS or SB modified surfaces alone, even at low functionalization concentrations. The antiadhesive and antibacterial properties of functionalized surfaces were investigated by challenging the surfaces against the bacterium Escherichia coli. All dual-functionalized coatings showed equal or reduced bacterial adhesion compared to QAS and SB functionalizations alone, while coatings functionalized with high concentrations of combined chemistries reduced the adhesion of bacteria by up to 95% compared to control SiNP surfaces.