In vitro, LL dose-dependently mitigated TBHP-induced damage via regulating oxidative stress and apoptotic pathways, reversed TBHP-induced EGR1 upregulation, EGR1 knockout enhanced oxidative stress resistance, and EGR1 directly regulated sprouty RTK signaling antagonist 4 (SPRY4) transcription, while LL inhibited TBHP-induced SPRY4 upregulation.<h4>Conclusion</h4>Luteolin protects against NIHL by alleviating oxidative stress and suppressing apoptosis, with potential involvement of the EGR1/SPRY4 signaling axis, representing a promising candidate for NIHL prevention. This evidence concerns the gene SPRY4 and noise induced hearing loss.