8-oxoguanine-DNA glycosylase (OGG-1) is a base excision DNA repair enzyme; however, its function in modulating allergic diseases remains undefined. Using OGG-1 knockout (KO) mice, we show that this protein impacts allergic airway inflammation following sensitization and challenge by ovalbumin (OVA). OGG-1 KO mice exhibited less inflammatory cell infiltration and reduced oxidative stress in the lungs after OVA challenge compared to WT mice. The KO phenotype included decreased IL-4, IL-6, IL-10, and IL-17 in lung tissues. In addition, OGG-1 KO mice showed decreased expression and phosphorylation of STAT6 as well as NF-κB. Down-regulation of OGG-1 by siRNA lowered ROS and IL-4 levels but increased INF-γ production in cultured epithelial cells following exposure to house dust mite (HDM) extracts. OGG-1 may affect the levels of oxidative stress and proinflammatory cytokines during asthmatic conditions. OGG-1-deficiency negatively regulates allergen-induced airway inflammatory response.