Objective: A polymorphism of gene p53 codon 72 is associated with various cancer formations. Tumor necrosis factor-α(TNF-α) one of the cytokines secreted by macrophages in response to inflammation and is also related to cancer formation. We aimed to evaluate the association between prostate cancer and the polymorphisms of the TNF-α gene promoter -308 and p53 gene codon 72. Patients and Methods: In our study, a normal control group of 126 healthy people and 96 patients with prostate cancer were examined. The polymorphism (G/A) of TNF-α gene was detected by polymerase chain reaction (PCR)-based restriction analysis (Nco I endonuclease) and the polymorphism of p53 gene was detected by two PCRs (one for proline and one for arginine form). Results: There was a significant difference in the distribution of codon 72 polymorphism the p53 gene between prostate cancer patients and the normal controls (p < 0.001). The proline form of p53 gene codon 72 was significantly higher than the arginine form, with an odds ratio of 2.606 (95% CI = 1.052-6.455). This difference was also revealed in the tumor staging (p = 0.035) as the proline form was significantly higher in the metastasis group of prostate cancer. There were no statistical differences in the distribution of -308 polymorphism of the TNF-α gene between cancer patients and the control subjects (p = 1.0). Conclusion: Prostate cancer appears to be associated with the p53 gene codon 72 polymorphisms, but not with the TNF-α gene. The proline form of p53 gene codon 72 might be a more significant risk factor for the development of metastasis than the arginine form.