Purpose: Dermatophagoides pteronyssinus (Der-p) 1, a cysteine protease, is a significant allergen derived from house dust mite (HDM) leading to the allergic immune response in HDM atopic individuals. Nowadays, HDM allergens are thought to play a role in the innate immunity in addition to the allergen-specific responses. The potential phosphoinositide 3-kinase (PI3K) inhibitors including PI3K-delta-targeting agents for asthma treatment have recently emerged. However, the role of PI3K-delta isoform is still controversy in airway epithelium under HDM-induced allergic response. This study aimed at the role of epithelial PI3K-delta isoform in HDM-induced allergic responses including NLRP3 inflammasome activation, focusing on the activation of airway epithelium. Methods: we used wild type (WT) mice and PI3K-delta knock-out (KO) mice for HDM-induced asthma animal model and also performed in vitro experiments using primary cultured murine tracheal epithelial cells and human airway epithelial cells. Results: Our results showed the significantly increased expressions of PI3K-delta isoform as well as NLRP3 inflammasome components in Der-p1-stimulated airway epithelial cells and the HDM-induced increases of epithelial cell-derived cytokines, IL-25, IL-33, and TSLP in lung tissues and airway epithelial cells. These increases were markedly suppressed by blockade of PI3K-delta, while the epithelial cell-derived cytokines levels did not respond to the NLRP3 inflammasome inhibitor. In addition, PI3K-delta KO mice and HDM-inhaled mice treated with PI3K-delta inhibitor exhibit the significant reduction of allergic asthmatic features especially mucus production of airway epithelium and the suppression of NLRP3 inflammasome assembly as well as epithelial cell-derived cytokines. Conclusion: These findings indicate that Der-p1 can promote type 2 airway epithelial activation with mucus production through PI3K-delta-isoform linked to the allergic airway inflammation including one of the innate immune responder, NLRP3 inflammasome activation.