Background: It has been hypothesised that vitamin D receptor (VDR) gene polymorphisms may influence both the risk of cancer occurrence and prognosis. Materials and Methods: The distribution of VDR Tag I polymorphism in 64 patients with OSCC was determined by polymerase chain reaction based restriction fragment length polymorphism (RFLP) and compared with that of 87 healthy controls. Results: There was a significant difference in the distribution of VDR Taq I genotypes between OSCC patients and healthy controls. Patients with the VDR Tt genotype were found to be at significantly higher risk for OSCC than those with other genotypes (p=0.036). In particular, female OSCC patients were at higher risk (p<0.001) for oral cancer. Conclusion: These results suggest that the VDR Taq I polymorphism may be associated with susceptibility to OSCC. Female predilection of the OSCC risk in association with VDR gene polymorphism should also be investigated.