RECQL is a DNA helicase involved in DNA mismatch repair. Previous studies indicated that the RECQL gene mutation was associated with human cancers. In the present study, we investigated the association between polymorphisms of RECQL gene and laryngeal cancer in a Chinese population. Four polymorphisms of the RECQL5 gene (rs820186, rs820196, rs820200, and rs4789223) were genotyped by the TaqMan method in 275 patients with larynx cancer and 300 age- and sex-matched non-cancer controls. We found that rs820196 polymorphism of RECQL5 was associated with larynx cancer, the CC genotype (16.4% vs 9.3%, P = 0.013) and C allele (42% vs 34.2%, P = 0.006) was common in larynx cancer patients than in the control subjects, respectively. Haplotype analysis showed that GCGA (OR = 18.955, 95% confidence interval (CI) 9.479 ~ 37.905; P < 0.001) and GTTG (OR = 1.684; 95% CI 1.327 ~ 2.137; P < 0.001) were associated with increased risk for larynx cancer. However, ACGA (OR = 0.605; 95% CI 0.430 ~ 0.852; P = 0.003), GCGG (OR = 0.636; 95% CI 0.411 ~ 0.982; P = 0.039), and GTGG (OR = 0.194; 95% CI 0.104 ~ 0.361; P < 0.001) were associated with decreased risk for larynx cancer. The present study indicated that RECQL5 genetic polymorphism and haplotypes were associated with larynx cancer in a Chinese population.