Abstract: Fas apoptotic inhibitory molecule a (FAIMa) is an anti-apoptotic protein that plays a crucial role in negative regulation of Fas receptor-mediated apoptotic signaling pathway. To investigate the role of FAIMa in the immune response of large yellow croaker (Larimichthys crocea), in the present study, a faima gene (named as Lcfaima) from large yellow croaker was obtained and identified. The expression profiles of Lcfaima in different tissues of large yellow croaker and its transcriptional expression responses in main immune tissues and cells to immune challenge were determined using quantitative real-time PCR (qPCR). Additionally, an overexpression plasmid pcDNA3.1-Lcfaima was constructed and the function of it in NF-κB activation was investigated. The results showed that the open reading frame (ORF) of Lcfaima was 546 bp, which encoded a 181-amino acid polypeptide with a calculated molecular weight of 20.21 kDa and a theoretical isoelectric point of 5.04. The predicted LcFAIMa contained a conserved FAIM1 domain (4-179 aa) characteristic of the FAIM1 family. Multiple alignments analysis showed that the predicted LcFAIMa shared high identities with 61-81% to the FAIM1/FAIMa homologs from human and other teleosts. The constitutive expression of Lcfaima was determined in all tissues examined with the most predominant expression in brain. The transcriptional expression of Lcfaima was significantly induced in most immune tissues after pathogenic bacteria Pseudomonas plecoglossicida challenge in vivo and in immune cells after LPS challenge in vitro (P < 0.05). Dual luciferase reporter assay system revealed that no significant change of NF-κB luciferase activity was detected after overexpression of LcFAIMa alone whereas the Fas-associated death domain protein (FADD)-mediated NF-κB activation was significantly suppressed by LcFAIMa. These findings suggested that LcFAIMa might be involved in immune responses in large yellow croaker by suppressing FADD-mediated NF-κB activation. This study is important for better understanding the teleost immune response.