| Summary: | <i>Phytophthora capsici</i> is one of the devastating pathogens, causing foliar blight, root rot, and fruit rot in peppers. Cinnamaldehyde (CA) is a natural compound coming from <i>Cinnamomum cassia</i>. The medicinal properties of CA have been widely identified. Limited knowledge is known about the application of CA in agriculture. In this study, CA significantly inhibited <i>P. capsici</i>, which further suppressed Phytophthora blights in both pepper seedlings and pepper fruits. Treatment with CA resulted in collapsed and fragmented hyphae, accompanying the increase in MDA (malondialdehyde) content and the decrease in intercellular glycerol content in hyphae. CA also inhibited the growth of wild type yeast. The yeast mutant Δ<i>Yvc1</i> with a deletion of Yvc1 (a Ca<sup>2+</sup> transporter) showed decreased sensitivity to CA. The transformation of <i>PcNCX1</i>, a sodium/calcium exchanger from <i>P. capsici</i>, into Δ<i>Yvc1</i> restored its sensitivity to CA. The transformant carrying <i>PcNCX1</i> also showed restored Ca<sup>2+</sup> efflux upon CA treatment. RNA-seq analysis showed that CA treatments resulted in the down-regulation of a set of genes encoding for calcium-related proteins. Collectively, our study demonstrates that the antifungal activity of CA against <i>P. capsici</i> may be associated with PcNCX1-mediated Ca<sup>2+</sup> efflux. Our results provide crucial insights into the antimicrobial action of CA.
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