Sound pollution (noise) is an increasing environmental concern, particularly associated with neurological and neurobehavioral abnormalities. However, the molecular mechanisms underlying noise-induced neural damage remain unclear. In this study, we conducted transcriptional profiling of zebrafish to investigate the mechanisms underlying acoustic stimulation (1,000 Hz, 130 dB). RNA sequencing and subsequent experiments revealed that TRPV1 is an important mediator of noise-induced neural damage in HuC(elavl3)-GFP transgenic zebrafish. The results demonstrated that inhibiting TRPV1 significantly mitigated noise-induced neural damage in zebrafish with trpv1 gene RNAi and in mice with Trpv1 knockout (Trpv1