Objectives: NIHL is a disease with irreversible damage caused by multi-factor interaction, and the STAT3 is an essential protein with signal transduction and transcription functions. This study is aimed to explore the effect of STAT3 polymorphism on individual susceptibility to NIHL individuals, and to further examine the interaction between lifestyles and NIHL in the dominant model .Methods: This study was designed a case-control study and included 609 NIHL cases and 611 healthy hearing controls from the Jiangsu province of China. By collecting the lifestyle and demographic information of the study participants, genotyping the collected blood samples, and performing Real-time Quantitative PCR (qRT-PCR) to analyze and investigate the potential association between STAT3 SNPs and NIHL.Results: Statistical analysis results show that individuals carrying the C allele of rs1053023 and rs1053005 were more likely to develop NIHL than individuals carrying the T allele (OR = 1.367, 95% CI = 1.148-1.628, P = 0.0001 and OR = 1.37, 95% CI = 1.147-1.636, P = 0.001). In the dominant model (TC/CC genotype and TT genotype), stratified analysis of lifestyle, we found that people who smoke regularly are more likely to suffer from NIHL than non-smokers or occasional smokers. Besides, the expression of STAT3 was higher in NIHL cases by real-time quantitative PCR.Conclusion: Gene polymorphisms, rs1053023 and rs1053005, from STAT3, are associated with NIHL and C alleles of rs1053023 and rs1053005 within STAT3 may become biomarkers for workers exposed to noise.