Objective: The aim of this case-control study was to explore whether five tagging single nucleotide poly- morphisms (tSNPs) within the transforming growth factor-ill (TGF-fll) gene were involved in manifestation of inflammatory and fibrotic processes associated with coal workers pneumoconiosis (CWP). Methods: The study included 508 CWP patients and 526 controls who were underground coal miners from Xuzhou Mining Business Group. Five tSNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The single SNP analysis showed that the genotype frequencies of SNP2 (rs1800470, +869T/C, extron 1) and SNP5 (rs11466345, intron 5) in CWP cases were significantly different from those in controls. Multivariate logistic regression analysis revealed that SNP2 (rs1800470) CC genotype was associated with decreased risk of CWP (OR = 0.50, 95% CI = 0.32-0.78), which was evident among subgroups of those never smoke (OR = 0.40, 95%CI = 0.24-0.66), cases with stage Ⅱ(OR = 0.41, 95%CI = 0.22-0.76) and exposure period (〈 28 y: OR = 0.54, 95%CI = 0.31-0.95; ≥ 28 y: OR = 0.52, 95%CI = 0.32-0.96). However, the SNP5 (rs11466345) GG genotype was associated with an increased risk of CWP (OR = 2.5, 95%CI = 1.36-4.57), and further stratification analysis showed that the risk of CWP was increased in both smoking and nonsmoking groups, shorter and longer exposure groups, while the risk of CWP was only increased in patients with stage I and Ⅱ. Conclusion: This study suggests that TGF-β1 polymorphisms may contribute to susceptibility of CWP.