Objective: To investigate the associations between genetic polymorphisms of GSTT1, GSTM1, GSTO1, GSTP1 and MTHFR genes and the DNA damage levels of BRCA1 and BRCA2 genes. Methods: Peripheral blood samples were used to measure DNA damage levels and genetic polymorphisms, and urine samples were collected to analyze arsenic metabolites in 79 arsenic-exposed workers and 24 non–arsenic-exposed workers. Results: The BRCA1 and BRCA2 damage levels in exposure group were significantly higher than that in control group. Significant associations were detected between GSTT1 and GSTO1 polymorphisms and DNA damage levels of BRCA1 and BRCA2 genes in subjects (P < 0.05). Conclusions: Our findings suggest that the DNA damage levels of BRCA1 and BRCA2 genes may modulate by genetic variations of GSTT1 and GSTO1 when individuals are exposed to carcinogens, such as arsenic.