DNA repair systems are indispensable for maintaining genomic integrity. Inherited polymorphisms of DNA repair systems related repair genes may contribute to individual variations in genetic susceptibility to oral cancer. We carried out a hospital-based case-control study to investigate the association of eight various polymorphisms in five DNA repair genes (XRCC1, XPA, XPC hMLH1 and XRCC3) with the risk for oral squamous cell carcinoma (OSCC). A total of 144 newly diagnosed OSCC and 215 frequency-matched controls were recruited between November 2003 and October 2004 at Kaohsiung Veterans General Hospital. Genotyping was performed using the PCR-RFLP techniques. In our results, we found that the XPA A23G polymorphism was strongly associated with OSCC risk (p for linear trend, 0.030) especially combined with XPC (p for linear trend, 0.026). Moreover a trend toward increased risk of OSCC was found when with the increasing putative high-risk genotypes of DNA repair genes (p for linear trend, 0.007). Therefore, we suggested that these polymorphisms in five repair genes were associated with the risk of OSCC. Furthermore, to investigate the prognosis of buccal carcinoma (BC), the most common site of oral cancer in Taiwan, we identified the protein expressions of XRCC1 and XPA and evaluated the relationship between expression level of proteins with clinicopathologic characteristics and survival outcome. A total of 138 primary BC specimens were recruited at KSVGH between 1994 and 2005 and the protein expression levels were identified by use of immunocytochemistry. The overall cumulative 5-years survival rate, 10-years survival rate and 12-years survival rate of BC patients were 66%, 55% and 44%, respectively. Survival curve of BC was significantly correlated with pathological stage, tumor size, lymph node metastasis, tumor differentiation, post-operative RT or CT. However, there were no significant differences between the survival curves of BC patients and the expression levels of XRCC1 and XPA, either in the univariate or the multivariate analysis. In conclusion, the combined effect of seven polymorphisms in five repair genes was associated with the risk of OSCC. However, the expression levels of XRCC1 and XPA were not associated with the survival for patients with BC.