Background: Notch signaling is important in keloid scar formation by regulating TGF-β pathway. I nflammasomes are involved in innate immune response, but the role is not known in the pathogenesis of keloid. Objectives: We intended to investigate whether the Notch signaling affects the activation of inflammasomes in keloid fibroblasts. Methods: Using mRNA and protein expression of inflammasomes NACHT, LRR and PYD domainscontaining protein 3 (NALP3) and ASC and proinflammatory cytokines, caspase-1 and IL-1b in the primary keloid fibroblasts was investigated. Notch-siRNA transfected keloid fibroblast cell line was used to examine the effect of Notch signaling. Results: Notch and NLRP3 inflammasome expression of keloid fibroblasts were enhanced. To find a cause of increased Notch and inflammasome expression, autophagy in keloid fibroblasts was examined. Autophagy was decreased in keloid fibroblasts and autophagy reflux analysis showed that decreased autophagic activity resulted in a reduction of Notch and inflammasome degradation in keloid fibroblasts. Notch silencing suppressed reactive oxygen species, NF-kB, α-smooth muscle actin, NLRP3, and caspase1. Conclusion: The present study demonstrated that Notch signaling involve in inflammasome-activation as well as fibrotic extracellular matrix production, and the clinical use of Notch inhibition may be useful treatment or prevention option for keloid.