AIM This study was aimed to determine whether serum thirodoxine reductase (TR) levels would be a prognostic marker or risk assessment factor in patients with prostate cancer and to investigate whether it could differentiate prostate cancer (PCa) from benign prostate hyperplasia (BPH). PATIENTS AND METHODS  We enrolled 35 patients with PCa subclassified into 2 groups (group1 PCa: 11 patients with Prostate specific antigen (PSA) less than 10 ng/ml and group2 PCa: 24 patients with PSA more than 10 ng/ml)), 42 patients with BPH, and 27 healthy individuals. Serum TR and PSA levels was measured by ELISA and was compared among all groups. All statistical analyses were calculated using ANOVA software and graph pad prism version 6. RESULTS  We found statistically significantly increased levels of TR in serum of patients diagnosed with PCa (group 1 and 2 PCa) vs. patients with BPH and healthy subjects at P≤0.0001 while there was no significant difference in PSA level between group 1 PCa and control (BPH and healthy) CONCLUSION The assessment of serum TR in addition to PSA appears to be of great benefit for a more accurate differential diagnosis of BPH and PCa.