Keratinocytes have been recognized to actively participate in the skin immune response. It has been shown that keratinocytes express all components that are necessary to form the NLRP3 inflammasome complex including the adapter protein ASC and caspase-1. In this study, we investigated the presence and activity of the recently identified absent in melanoma 2 (AIM2) inflammasome in human keratinocytes. We were able to show that an AIM2 inflammasome is active in human keratinocytes. IL-1 production by keratinocytes plays a pivotal role in inflammatory processes in the skin. Activation of the AIM2 inflammasome in keratinocytes represents another potential trigger factor for the development and maintenance of inflammatory skin diseases.