Background: Squamous Cell Carcinoma (SCC) is the second most common malignancy of the respiratory tract. Recently, researchers believe that thioredoxin system is effective in the cancerization of some tissues. Thus, this study has been conducted with the aim of measuring of thioredoxin reductase (TrxR) enzyme activity and tissue distribution in the pathologic specimens of patients with laryngeal SCC.Materials and Methods: This study was performed on 40 pathologic blocks (20 healthy and 20 tumoral) from 20 patients with laryngeal SCC who were candidates for laryngectomy surgery. The TrxR enzyme activity was measured by the commercial kit. Also, the tissue distribution of TrxR was determined by immunohistochemical staining and the percentage of staining cells (SC%) and staining intensity were calculated. Data were analyzed by using SPSS13 and significant level was set at P≤0.05.Results: The average the TrxR enzyme activity in the healthy and tumoral tissues was 0.004±0.003µM/min/ml and 0.006±0.003µM/min/ml, respectively (ranged 0.0009 to 0.0104 vs. 0.001 to 0.011 ). However, there was no relationship between the TrxR enzyme activity in the tumoral and healthy tissues (P=0.084). The total score of IHC staining in the healthy tissue was 4.45±1.09 whereas the total of these scores in the tumoral tissue 6.25±0.63. The both scores of SC% and staining intensity in the tumoral tissue was significantly higher than the healthy tissue (P<0.001).Conclusion: Based on the results, although the TrxR enzyme activity has not the significant differences in tumoral tissue compare to healthy tissue, but the tissue distribution in tumoral tissue was higher than healthy tissue.[GMJ.2016;5(3):153-159]