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The liver is a multi-functional organ including metabolism, substance synthesis, detoxification, and various immune functions, and its role in immunity has attracted more and more attention. However, research on the liver immune response of fish infected by pathogenic bacteria is currently lacking. In this study, the transcriptomics and proteomics of the liver of Cynoglossus semilaevis infected with Vibrio anguillarum were analyzed. A total of 1470 genes and 497 proteins were differentially expressed in the pairwise comparison of obvious symptoms of infection (HOSG), no obvious symptoms of infection (NOSG) and PBS treatment (CG). Gene ontology and KEGG enrichment pathways analysis showed that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were mainly enriched in toll-like receptors (TLRs), complement and coagulation cascades, nucleotide oligomerization domain (NOD)-like receptors (NLRs), mitogen-activated protein kinase (MAPK) and phagosome signaling pathways, which suggested the combined action of the five pathways were significant to enhance the liver immune defense. The combination of transcriptomic and proteomic analysis showed that ITGβ1 , C3 , C5 and MRC1 were significantly up-regulated, which might play an important role in the liver immune response to the recognition of V. anguillarum , inflammatory response and phagocytosis. The transcriptome and proteome data we obtained provide information on some key genes and proteins for further study of the mechanism of liver immune response. [Display omitted] • There were 1470 DEGs and 497 DEPs in C. semilaevis after V. anguillarum infection. • PRRs, MAPK, phagosome and complement pathways in the liver were significantly altered. • Transcriptomic/proteomic analysis showed up-regulation of ITGβ1 , C3 , C5 and MRC1. [ABSTRACT FROM AUTHOR]