Betel quid¡]BQ¡^chewing is recognized as a major risk factor for oral precancerous lesions¡]OPLs¡^in Taiwan. The compositions of Betel quid could cause DNA damage. X-ray repair cross complementing Group 1¡]XRCC1¡^plays a crucial role in the process of DNA repair. Polymorphisms in XRCC1 gene may affect DNA repairing ability and modulate the susceptibility of OPLs. The aim of this study was to investigate the association of XRCC1 genetic variants with the risk of BQ-related oral precancerous lesions, including oral leukoplakia¡]OL¡^ and oral submucous fibrosis ( OSF ). A total of 449 males¡]169 OL cases, 82 OSF cases, and 208 healthy controls¡^who habitually chewed BQ were recruited. The genotypes were determined by PCR-RFLP and TaqMan real-time assays. The C allele and T/C+C/C genotypes at XRCC1 -77 were associated with the reduced risk of OL ( AOR=0.54, 95%CI:0.34-0.85 and AOR=0.47, 95%CI:0.28-0.78, respectively ). The 399Gln allele and 399 Arg/Gln+Gln/Gln genotypes were associated with the increased risk of OL¡]AOR=1.94; 95%CI: 1.41-2.67 and AOR=2.64; 95%CI: 1.73-4.03, respectively¡^and OSF ( AOR=1.67; 95%CI: 1.11-2.49 and AOR=2.30; 95%CI: 1.35-3.91, respectively ). The haplotypes or diplotypes contain fewer risk alleles¡]-77T or 399Gln¡^ were with lower risk of OL¡]both Ptrend<0.001¡^and OSF (Ptrend=0.056 and Ptrend=0.040, respectively). In conclusion, our results suggest that polymorphisms of XRCC1 at -77 and 399 may be associated with the risk of OPLs.