In mammals, long non-coding RNAs (lncRNAs) play a regulatory role in gene expression, contribute to immune responses, and aid in pathogen elimination, primarily through interactions with RNA-binding proteins (RBPs). However, the role of lncRNAs in fish innate immunity and their interaction with RBPs remains uncertain. To investigate the immunomodulatory role of lncRNAs in Megalobrama amblycephala, we identified the novel lncRNA MSTRG.59348.1 and examined its function in the innate immune response to Aeromonas hydrophila infection. Localization studies in hepatocytes revealed that MSTRG.59348.1 is primarily located in the nucleus, suggesting its potential involvement in gene regulation, possibly through chromatin modification or other nuclear processes. The expression of MSTRG.59348.1 was significantly up-regulated after lipopolysaccharide (LPS) stimulation in liver cells. RNA-seq analysis of muscle cells revealed that genes differentially expressed following MSTRG.59348.1 overexpression were enriched in immune pathways. MSTRG.59348.1 overexpression significantly inhibited the expression of sting and ifn, and significantly up-regulated muscle cell viability and promoted cell proliferation by targeting sting, ifn, nf-κb1, and bcl2. Screening by RNA pull-down and mass spectrometry identified 57 RBPs interacting with MSTRG.59348.1, with functions enriched in immune pathways. Our results suggest that MSTRG.59348.1 plays a crucial regulatory role in fish antibacterial response, marking it as a significant subject for future research in innate immunity.