Coal workers' pneumoconiosis (CWP) is a chronic interstitial lung disease with a complex etiology that can occur after cumulative dust exposure. A case-control study was conducted to test the hypothesis that single-nucleotide polymorphisms (SNP) within CASPASE-8 (CASP8) promoter involved in resolution of inflammatory processes modulate the risk of CWP development. The study population consisted of 619 underground coal miners in the 5 coal mines of Xuzhou Mining Business Group Co. Ltd., China, of whom 315 were diagnosed with CWP. The association study between CASP8 -652 6N ins/del polymorphism with CWP by multiple logistic regression analysis showed a significant association of the genotype del/del with CWP compared with to ins/ins genotypes, and showed that the risk was significantly higher for stage I CWP. Further analysis showed that in subjects with the del/del genotype there was significantly increased risk for CWP occurrence among younger individuals (<66 yr) or those with longer duration dust exposure (>or=26 yr). These findings suggested that CASP8-652 6N ins/del polymorphism may contribute to the genetic susceptibility for CWP development.