The detection and monitoring of colorless and odorless chemical warfare agents (CWAs) has become important due to the increasing threat of terrorist activities. To enhance the sensitivity and selectivity of CWAs a number of sensing materials have been developed, including the widely used polyvinylidene fluoride (PVDF). However, PVDF is limited by its low sensitivity and selectivity for many CWAs. In this study, polyhedral oligomeric silsesquioxane (POSS) was used as a sensing material for dimethyl methylphosphonate (DMMP) a simulant of sarin nerve gas. Sensitivity, selectivity, and reusability were investigated with an AT-cut 5 MHz quartz crystal microbalance. At room temperature, POSS exhibited a strong response for DMMP vapor at different concentrations from 20 ppm to 120 ppm leading to fast chemical adsorption and desorption. To investigate selectivity the volatile organic compounds (VOCs) ethanol, water, toluene, ACN, methanol, and n-hexane were tested at a fixed flow rate. Targeted VOCs showed lower responses than DMMP as measured with a quartz crystal microbalance (QCM) sensor, demonstrating the high selectivity of the method. POSS can be considered a potentially useful material for sensing nerve simulants.