The CCR4-CAF1-NOT complex-mediated degradation of mRNA is a fundamental aspect of gene regulation in eukaryotes. We herein examined the role of AtCAF1 in the innate immune and wound responses of plants. Our results showed that overexpression of AtCAF1 significantly down-regulated the transcript level of EFR but not FLS2 and BRI1, as well as abolished up-regulated expression pattern of EFR in response to wounding. Consistently, Agrobacterium-mediated transient expression of GUS was highly enhanced in the transgenic plants overexpressing AtCAF. Furthermore, JA responsive genes were down-regulated by overexpression of AtCAF, causing the transgenic plants overexpressing AtCAF more susceptible to necrotrophic fungal pathogen, Botrytis cinerea. These results suggest that The CCR4- CAF1-NOT complex-mediated degradation of mRNA negatively regulates wounding-mediated disease resistance in Arabidopsis thaliana.