House dust mites (HDM) are one of the commonest aeroallergens worldwide. Specifically, NLRP3 is one of PRR systems activated by HDM extract in airway epithelial cells. In this study, we have investigated the effects of IC87114, a representative inhibitor of PI3K-δ isoform, on the HDM-induced airway inflammation and hyperresponsiveness, focusing on NLRP3 inflammasome activation and its related molecular mechanisms. HDM-sensitized and -challenged mice showed the typical allergic airway inflammation and hyperresponsivenss, the increased levels of Th2 cytokines, IL-17, IL-1β, and TNF-α in lungs, and increased levels of GSSG and decreased levels of GSH in lung tissues. Moreover, we found the increases of mitochondrial ROS and the NLRP3 inflammasome activation in HDM-exposed lung. Very interestingly, the administration of IC87114 restored the levels of GSH, decreased the numbers of airway inflammatory cells in BAL fluids, the peribronchial and perivascular inflammation in lung tissues, the increase in the levels of inflammatory cytokines, the levels of mitochondrial ROS, NLRP3 activation, and bronchial hyperresponsiveness in HDM-sensitized and -challenged mice. Primary cultured tracheal epithelial cells from HDM-inhaled mice showed the increased expression of NLRP3, IL-1β, and caspase-1 compared to the levels in cells from control mice. These findings suggest PI3K-δ plays an important role in HDM-induced bronchial asthma through the regulation of NLRP3 activation mediated by mitochondrial ROS.House dust mites (HDM) are one of the commonest aeroallergens worldwide. Specifically, NLRP3 is one of PRR systems activated by HDM extract in airway epithelial cells. In this study, we have investigated the effects of IC87114, a representative inhibitor of PI3K-δ isoform, on the HDM-induced airway inflammation and hyperresponsiveness, focusing on NLRP3 inflammasome activation and its related molecular mechanisms. HDM-sensitized and -challenged mice showed the typical allergic airway inflammation and hyperresponsivenss, the increased levels of Th2 cytokines, IL-17, IL-1β, and TNF-α in lungs, and increased levels of GSSG and decreased levels of GSH in lung tissues. Moreover, we found the increases of mitochondrial ROS and the NLRP3 inflammasome activation in HDM-exposed lung. Very interestingly, the administration of IC87114 restored the levels of GSH, decreased the numbers of airway inflammatory cells in BAL fluids, the peribronchial and perivascular inflammation in lung tissues, the increase in the levels of inflammatory cytokines, the levels of mitochondrial ROS, NLRP3 activation, and bronchial hyperresponsiveness in HDM-sensitized and -challenged mice. Primary cultured tracheal epithelial cells from HDM-inhaled mice showed the increased expression of NLRP3, IL-1β, and caspase-1 compared to the levels in cells from control mice. These findings suggest PI3K-δ plays an important role in HDM-induced bronchial asthma through the regulation of NLRP3 activation mediated by mitochondrial ROS.