P. yezoensis is an economically important marine crop and highly used seafood in China containing a high number of proteiP. yezoensis is an economically important marine crop and highly used seafood in China containing a high number of proteins. An oomycete, known as Pythium porphyrae, causes the red rot disease that seriously damages Pyropia farms every year in China, Korea, and Japan. To investigate the pathogen responsive proteins after the artificial infection of Pyropia with (P. porphyrae) oomycetes spores, an iTRAQ-based proteomic analysis was performed. A total of 762 differentially expressed proteins (DEP’s) were identified from which 378 proteins were highly expressed and 284 proteins were found to be low expressed. A large number of differentially expressed proteins were identified, which are involved in disease stress, carbohydrate metabolism, photosynthetic activity, and amino acid pathways as annotated in the Kyoto Encyclopedia of Genes and Genomes KEGG database. Our results showed that Pyropia resisted infection by inhibiting photosynthesis, energy and carbohydrate metabolism pathways, as supported by the change in the expression level of related proteins. Thus, the current research data provide an overall summary of the red algae response to pathogen infection. The present study could assist in a better understanding of the mechanisms behind infection resistance in P. yezoensis as well as improve the breeding of Pythium infection tolerant macroalgaens. An oomycete, known as Pythium porphyrae, causes the red rot disease that seriously damages Pyropia farms every year in China, Korea, and Japan. To investigate the pathogen responsive proteins after the artificial infection of Pyropia with (P. porphyrae) oomycetes spores, an iTRAQ-based proteomic analysis was performed. A total of 762 differentially expressed proteins (DEP’s) were identified from which 378 proteins were highly expressed and 284 proteins were found to be low expressed. A large number of differentially expressed proteins were identified, which are involved in disease stress, carbohydrate metabolism, photosynthetic activity, and amino acid pathways as annotated in the Kyoto Encyclopedia of Genes and Genomes KEGG database. Our results showed that Pyropia resisted infection by inhibiting photosynthesis, energy and carbohydrate metabolism pathways, as supported by the change in the expression level of related proteins. Thus, the current research data provide an overall summary of the red algae response to pathogen infection. The present study could assist in a better understanding of the mechanisms behind infection resistance in P. yezoensis as well as improve the breeding of Pythium infection tolerant macroalgae