Objective To test whether polymorphisms in IL-1, NF-KB, FAS, and FASL genes are associated with risk of silicosis. Methods A case-control study was conducted with 183 silicosis patients and 111 silica-exposed miners who were frequency-matched by age, dust exposure duration, work location, and type of work. Genotype analysis was performed on genomic DNA, using a PCR-RFLP assay. Results Individuals carrying the NFKB1 ins/del genotype had a decreased risk of silicosis (adjusted OR = 0.57, 95% CI = 0.32-0.998, P = 0.049) compared with subjects carrying the ins/ins genotype and individuals with the FAS-1377AA homozygote had a decreased risk of silicosis compared with those with the - 1377GG genotype (adjusted OR = 0.42, 95% CI = 0.19-0.93, P = 0.03). The analysis of haplotypes of polymorphisms in FAS fold (OR = 2.71, 95% CI = 1.22-6.03, P = 0.011) increased risk of silicosis for subjects with alleles of FAS-1337G and FAS-670G, compared with those carrying alleles of FAS-1377G and FAS-670A. Conclusions Although the polymorphisms at NFKB1, FAS-1377, and extended haplotype FAS-1377G/-670G may play a role in the development of silicosis in the Chinese population, out-findings should be verified by larger studies with > 1 case/control ratio. Am. J. Ind. Med. 51:843-851, 2008. (C) 2008 Wiley-Liss, Inc.