Exposure to cigarette smoke (CS) is the main risk factor for developing COPD and can induce airway epithelial cell damage, innate immune responses and airway inflammation. We hypothesized that cell survival factors might decrease the sensitivity of airway epithelial cells to CS-induced damage, thereby protecting the airways against inflammation upon CS exposure. Here, we tested whether Pim survival kinases could protect from CS-induced inflammation. We determined expression of Pim kinases in lung tissue, airway inflammation and levels of Keratinocyte-derived Cytokine and several Damage-associated molecular patterns (DAMPs) in bronchoalveolar lavage in mice exposed to CS or air. Human bronchial epithelial BEAS-2B cells were treated with CS extract (CSE) in presence or absence of Pim1 inhibitor, and assessed for loss of mitochondrial membrane potential, induction of cell death and release of HSP70. We observed increased expression of Pim1, but not of Pim2 and Pim3 in lung tissue after exposure to CS. Pim1-deficient mice displayed a strongly enhanced neutrophilic airway inflammation upon CS exposure compared to wild-type controls. Inhibition of Pim1 activity in BEAS-2B cells increased the loss of mitochondrial membrane potential and reduced cell viability upon CSE treatment, while release of HSP70 was enhanced. Interestingly, we observed release of S100A8 but not of dsDNA or HSP70 in Pim1-deficient mice compared to wild-type controls upon CS exposure. In conclusion, we show that expression of Pim1 protects against CS-induced cell death in vitro and neutrophilic airway inflammation in vivo. Our data suggest that the underlying mechanism involves CS-induced release of S100A8 and KC.