The glutathione peroxidase 3 gene (GPX3) is reported to be a risk factor for arterial ischaemic stroke and cerebral venous thrombosis. GPX3 may be one of the aetiologies of sudden sensorineural hearing loss (SSNHL), which might be attributed to the genetic effect of GPX3 by influence reactive oxygen species (ROS). Unbalanced ROS have been associated with susceptibility to SSNHL. Therefore, we conducted a case-control study with 416 SSNHL cases and 255 controls. Five single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan genotyping assays. Each SNP was tested using the Hardy-Weinberg equilibrium (HWE), and the genetic effects were evaluated using three inheritance models. All five SNPs were in HWE. As the result, the AG genotype of rs3805435 had an adjusted odds ratio (OR) of 0.54 (95% confidence interval = 0.37-0.79, p = 0.001) compared with the AA genotype in the SSNHL cases. The GG and AG genotypes of the SNP rs3805435 were associated with SSNHL under the dominant model (p = 0.002, OR = 0.58). In conclusion, these results suggest that GPX3 polymorphisms influence susceptibility to SSNHL in southern Taiwan.