A quantitative characterization of the wetting states of droplets on hydrophobic textured surfaces requires direct measurement of the liquid penetration into surface cavities, which is challenging. Here, the use of quartz crystal microbalance (QCM) technology is reported for the characterization of the liquid penetration depth on a micropillar-patterned surface. The actual liquid-air interface of the droplet was established by freezing the droplet and characterizing it using a cryogenically focused ion beam/scanning electron microscope (cryo FIB-SEM) technique. It was found that a direct correlation exists between the liquid penetration depth and the responses of the QCM. A very small frequency shift of the QCM (1.5%) was recorded when the droplet was in the Cassie state, whereas a significant frequency shift was observed when the wetting state changed to the Wenzel state (where full liquid penetration occurs). Furthermore, a transition from the Cassie to the Wenzel state can be captured by the QCM technique. An acoustic-structure-interaction based numerical model was developed to further understand the effect of penetration. The numerical model was validated by experimentally measured responses of micropillar-patterned QCMs. The results also show a nonlinear response of the QCM to the increasing liquid penetration depth. This research provides a solid foundation for utilizing QCM sensors for liquid penetration and surface wettability characterization.