Conclusion Patients who carry the T/T homozygote of CYP17 C/T gene polymorphism may have a higher risk of developing oral cancer. Objective Cancer of the oral cavity is the most commonly seen malignancy in Taiwan, and its rising incidence poses a formidable challenge to oncologists. The CYP17 gene encodes P450c17alpha, an enzyme involved in the metabolism of steroid hormones. Tumor necrosis factor-α (TNF-α) is one of the cytokines produced by macrophages, and its function has been postulated to play a role in cancer formation. We investigated whether polymorphisms of CYP17 and TNF-α genes are associated with oral cancer. Material and methods Polymorphisms of CYP17 and TNF-α genes were detected by polymerase chain reaction-based restriction analysis in 137 patients with oral cancer and 102 normal controls. Results The results for the CYP17 gene revealed a significant difference between oral cancer patients and normal controls (p=0.0063), but there was no significant difference for the TNF-α gene (p=0.4753).