Simple SummaryOcean noise pollution from marine traffic may affect the behavioral, ecological and biochemical parameters of marine fish species. Most studies have focused on behavioral changes and hearing damage in fishes, but the molecular mechanism of noise exposure in the impairment of the brain has rarely been reported. In this study, using small yellow croaker (L. polyactis) as a model, we used RNA-seq methods to characterize differently expressed genes between the control group and the noise exposure group. GO and KEGG pathway analysis found that synaptic transmission, neurotransmitter transport, endocytosis procession, cell adhesion molecules and the extracellular matrix receptor interaction pathway were over-represented in the DEGs. In addition, behavioral studies revealed that L. polyactis kept motionless on the surface of the water and lost the ability to keep their balance after noise exposure. Collectively, our results indicate that exposure to noise stressors contributes to neurological dysfunction in the brain and impaired locomotor ability in L. polyactis.Noise has the potential to induce physiological stress in marine fishes, which may lead to all sorts of ecological consequences. In the current study, we used the RNA-sequencing (RNA-seq) method to sequence the whole transcriptome of the brain in small yellow croaker (Larimichthys polyactis). The animals were exposed to a mix of noises produced by different types of boat played back in a tank, then the brain tissues were collected after the fish had been exposed to a 120 dB noise for 0.5 h. In total, 762 differently expressed genes (DEGs) between the two groups were identified, including 157 up regulated and 605 down regulated genes in the noise exposure group compared with the control group. Gene ontology (GO) enrichment analysis indicated that the most up regulated gene categories included synaptic membranes, receptor-mediated endocytosis and the neurotransmitter secretion process. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways found that endocytosis, cell adhesion molecules and the extracellular matrix (ECM) receptor interaction pathway were over-represented. Specifically, ECM-related genes, including lamin2, lamin3, lamin4, coll1a2, coll5a1 and col4a5 were down regulated in the noise exposure group, implying the impaired composition of the ECM. In addition, the behavioral experiment revealed that L. polyactis exhibited avoidance behaviors to run away from the noise source at the beginning of the noise exposure period. At the end of the noise exposure period, L. polyactis kept motionless on the surface of the water and lost the ability to keep their balance. Taken together, our results indicate that exposure to noise stress contributes to neurological dysfunction in the brain and impaired locomotor ability in L. polyactis.