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In this case-control study, pathologically confirmed lung cancer patients and controls from the Chinese Han population were investigated to determine the effect of variant genotypes within the PSMA4 locus on susceptibility to lung cancer and sensitivity to cisplatin-based chemotherapy. METHODS: We identified validated tagged single nucleotide polymorphisms (tSNPs) with minor allele frequency >5 % in the HapMap Chinese Han Beijing population and genotyped seven SNPs within the PSMA4 locus. Their correlation with lung cancer risks and treatment response were examined using chi (2) test and haplotype analysis. Multivariate logistic regression analysis tested the association between the polymorphisms and chemotherapy response. RESULTS: rs12901682 is associated with lung cancer risks (OR = 1.45, 95 % CI, 1.04-2.02; P = 0.029). Using SNPStats software, we found rs12901682 (OR = 6.30, 95 % CI, 1.31-30.26; P = 0.0073) associated with lung cancer risks in the recessive model. Haplotype analysis showed that "CAGAATC" conferred an increased risk of lung cancer (OR = 1.50, 95 % CI, 1.07-2.11; P = 0.019). After adjustment for age, this association was pronounced in the male gender (OR = 6.30, 95 % CI, 1.31-30.26; P = 0.0073). PSMA4 polymorphisms did not affect the tumor sensitivity to cisplatin combination chemotherapy. CONCLUSIONS: Our study suggests a potential association between PSMA4 variants and lung cancer risk in Chinese Han population.