Lysyl oxidase (LOX) is an extracellular enzyme critical for the cross-linking of collagens and elastin. The LOX gene has also been shown to inhibit the transforming activity of Ras oncogene signaling. Recently, a single-nucleotide polymorphism (SNP) of LOX G473A (rs1800449) has been demonstrated to be associated with increased risk of breast cancer in African American women. In this hospital-based case-control study, the association of LOX polymorphism with breast cancer susceptibility in Chinese Han population was investigated. In total, 238 female patients with breast cancer and 234 age-matched healthy controls recruited were genotyped. We found a significant difference in the frequency of the LOX G473A genotype between the breast cancer and control groups. Individuals with GA genotype showed a 2.79-fold (95% confidence interval = 1.87-4.16) increased risk of breast cancer compared with subjects carrying GG genotype (p < 0.001). Further statistical analysis revealed that this polymorphism was an independent parameter with regard to other variables that are significantly associated with breast cancer, that is, age, menopausal status, estrogen exposure interval, expression status of estrogen receptor, and progesterone receptor. These findings suggest that the LOX 473 GA genotype is independently associated with increased risk of breast cancer in Chinese female population.