Over 90% of head and neck cancers are squamous cell carcinomas (HNSCC) and the overall 5-year survival rate is up to 50%. The redox status of these cancers is an important factor in carcinogenesis and plays a role in radioresistance and therefore locoregional recurrences. However, knowledge of the redox status is rather limited. Glutathione is the major reactive oxygen species scavenger in normal cells. We compared the levels of tissue redox potential in HNSCC tumor tissue and compared them with those of the adjacent, histologically cancer-free, mucosa. A total of 36 patients with HNSCC were included in the study. The redox status of tumor and normal adjacent tissue was measured by the oxidized/reduced glutathione (GSSG/GSH) ratio in capillary electrophoresis. The GSSG/GSH ratio in the tumor tissue was lower compared with adjacent normal tissue in 38% of the patients. Pretherapy HNSCC tumor tissue has variable GSH levels compared with adjacent cancer-free mucosa. This difference was not related to clinical and pathological parameters. Further studies are required to determine whether the GSSG/GSH ratio plays a role in carcinogenesis and could predict radioresistance.