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Objectives.The purpose of this study was to investigate the correlation between single-nucleotide polymorphism (SNP) in 3′UTR of XPO5 gene and the occurrence of noise-induced hearing loss (NIHL), and to further explore the regulatory mechanism of miRNAs in NIHL on XPO5 gene. Methods.We conducted a case-control study involving 1040 cases and 1060 controls. The effects of SNPs on XPO5 expression were studied by genotyping, real-time polymerase chain reaction (qPCR), cell transfection, and the dual-luciferase reporter assay. Results.We genotyped four SNPs (rs2257082, rs11077, rs7755135, and rs1106841) in the XPO5 gene. The rs2257082 AG/GG carriers have special connection to an increased risk of noise-induced hearing loss compared to the AA carriers. The rs11077TG/GG carriers had a significantly increased association with NIHL susceptibility than the TT carriers. There was a higher risk of NIHL in the XPO5 gene rs7755135 CC carriers than in the TT carriers. No statistically significant correlation was obtained with respect to SNPrs1106841. Functional experiments showed that the rs11077 change might inhibit the interaction between miRNAs (miRNA-4763-5p, miRNA-5002-3p, and miRNA-617) and XPO5, with rs11077G allele resulting in overexpression of XPO5. Conclusion. The genetic polymorphism, rs11077, within XPO5 is associated with the risk of noise-induced hearing loss in a Chinese population. [ABSTRACT FROM AUTHOR]