Impairment of fibrinolytic function plays an important role in the mechanism of thrombotic disorders in cancer patients. Thrombin-activatable fibrinolysis inhibitor (TAFI) has an antifibrinolytic effect as it can remove partially degraded fibrin C-terminal lysine residues and reduce plasmin formation. The purpose of this study was to investigate whether blood TAFI levels and TAFI Thr325Ile polymorphism could be a risk marker of breast cancer. The plasma TAFI antigen (Ag) level was determined using ELISA assay in 256 patients with breast cancer and 192 healthy controls. TAFI Thr325Ile (rs1926447) polymorphism was genotyped in both patients and control groups using PCR-restriction fragment length polymorphism (PCR-RFLP) and sequencing. The results showed that TAFI Ag levels were significantly higher in breast cancer patients than those in controls (100.6 ± 15.2 and 82.7 ± 11.2%, P < 0.001). TAFI Ag levels were correlated with metastasis of breast cancer (P < 0.001). The Thr/Ile (CT) and Ile/Ile (TT) genotypes were found more frequently in patients group compared with the control group [odds ratio (OR) 2.106; (95% confidence interval, CI 1.379-3.217); P < 0.001]. The high-risk T alleles frequency was also higher in patients compared with healthy controls [OR 1.718; (95% CI 1.316-2.243); P < 0.001]. The polymorphism was significantly correlated with TAFI Ag levels in either group (P < 0.001). The Ile/Ile (TT) genotype had the lowest TAFI Ag level, whereas the Thr/Thr (CC) had the highest one. In conclusion, the plasma TAFI levels and TAFI Thr325Ile genotypes were associated with breast cancer patients in Chinese Han populations and could be considered as the risk indicators of breast cancer.