Background Pollution, especially cigarette smoke, is a major cause of skin damage. Objectives To assess the effects of the small molecule polyphenol, honokiol, on reversing cigarette smoke-induced damage in vitro to relevant skin cells. Methods Keratinocytes (HaCat) cultures were exposed to cigarette smoke and, after 48 hours, IL-1 α and IL-8 were measured in cell supernatants. Moreover, TIMP-2 production, apoptosis rate, and senescence β-galactosidase expression were evaluated in primary human foreskin fibroblasts ( HFF-1) cultures. Results Honokiol at 10 μ m reduced IL-1 α production by 3.4 folds ( P < 0.05) and at 10 and 20 μ m reduced IL-8 by 23.9% and 53.1% ( P < 0.001), respectively, in HaCat keratinocytes. In HFF-1, honokiol restored TIMP-2 production by 96.9% and 91.9% ( P < 0.001), respectively, at 10 and 20 μ m, as well as reduced apoptosis by 47.1% ( P < 0.001) and 41.3% ( P < 0.01), respectively. Finally, honokiol reduced senescence-associated β-galactosidase expression in HFF-1. Conclusion Honokiol protects both HFF-1 and HaCat against cigarette smoke-induced inflammation, collagenolysis, apoptosis, and senescence. [ABSTRACT FROM AUTHOR]