SUMMARYThis study provides evidence that flg22, the most conserved 22‐amino acid peptide in the N‐terminal part of bacterial flagellin can trigger the defense responses of Pyropia haitanensis (Bangiales, Rhodophyta). The defense responses are a chain of events including release of H2O2 and free unsaturated fatty acids C20:4, consumption of C18:3, and the chemical or enzymatic oxidation of both C20 and C18 polyunsaturated fatty acids. Oxidized C20 and C18 fatty acids lead to the production of corresponding hydroperoxy and hydroxylated derivatives, such as 9‐hydroperoxy octadecadienoic acid, 8‐hydroperoxy eicosapentaenoic acid, and 8‐hydroxyl eicosapentaenoic acid, which could be further oxidatively metabolized to yield saturated aldehydes and ketone. Changes of three typical hormones jasmonate, methyl jasmonate, and salicylic acid were observed. Contrary to the increase of jasmonate and methyl jasmonate, salicylic acid was decreased. The expression of key enzymes of oxylipin pathway PhLOX and PhLOX2 were upregulated. However, some defense and antioxidant related genes including PhHsp 70, Phsod , and PhRboh were downregulated markedly at the early stage of flg22 challenge. Overall, our results imply that red algae have evolved a similar defense response and may share the conservative‐recognizing receptor for flg22 as in higher plants.