Novel silsesquioxane thin films were conveniently synthesized by the sol-gel route under mild conditions. Thus, a sol was prepared from 4,4′-bis(triethoxysilyl)-1,1′-biphenyl (4,4′-BTEBp) under a hydroalcoholic medium without a surfactant, deposited by spin-coating on silica supports, and dried at 280 °C. The resulting biphenylene-bridged films exhibited very smooth surfaces, excellent mechanical behavior and no cracks. Moreover, SEM and TEM studies showed flawless, homogeneous interfaces with silica substrates. The acoustic waveguide properties of these films on piezoelectric quartz microsensors were investigated at high frequency through a network analyzer. For an optimal thickness close to 1 μm, a marked frequency shift of the main broad lobe and a decrease of the insertion loss were observed. These results show a strong effect of the waveguide for trapping the acoustic energy, promising an unprecedented ability to provide a new generation of sensors. The capability of this device in the detection of mass is also demonstrated through the immobilization of Bovine Serum Albumin (BSA). This novel approach appears very promising in view of the development of surface acoustic wave sensors and biosensors.