The grainyhead like 2 (GRHL2) is a transcription factor, and the role among noise exposed workers is not well established. We tested whether GRHL2 polymorphisms are associated with the risk of noise-induced hearing loss (NIHL) in Chinese high intensity noise exposed workers. We genotyped six polymorphisms of GRHL2 gene (i.e., rs611419, rs3779617, rs3735713, rs3735714, rs3735715, and rs6989650) of 340 NIHL cases and 356 control subjects who exposed to noise higher than 85 dB (A) [Lex, 8 h=time-weighted average of levels of noise exposure (Lex) for a nominal 8 h working day] in a Chinese population. Compared with rs611419 AA genotype, the AT/TT genotypes conferred protection against NIHL [adjusted odds ratio (OR)=0.71, 95% confidence interval (CI)=0.52-0.98]. No altered NIHL risk was associated with the other five polymorphisms. In the combined analyses, we found that the combined genotypes with three to eight variant alleles were associated with an decrease risk of NIHL compared with those with zero to two variant alleles, and the decrease risk was more pronounced among subgroups of exposure time>20 yr (0.31, 0.16-0.62) and drinkers (0.51, 0.29-0.90). Polymorphisms of GRHL2 may positively contribute to the etiology of NIHL.