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This book is about the glutathione which is an important thiol compound that plays an important role in the antioxidant defense system required for the maintenance of redox status of the cell, defense against free oxygen radicals (ROS) and detoxification of toxic compounds. In the present study, we investigated the alterations of the glutathione levels in blood and tissue samples from patients with head and neck cancer. The results indicated that glutathione levels total and reduced, in the blood of head and neck cancer patients were significantly lowered as compared to respective controls. In contrast, the levels of glutathione total and glutathione reduced were significantly increased in tissues of patients with head and neck cancer compared to the tissues adjacent to cancer-free tissues used as controls. These changes in glutathione levels in blood and tumors of head and cancer may be due to increased utilization of glutathione due to variant genotypes and reactive oxygen species (ROS). We concluded that the glutathione levels in head and neck cancer patient's blood or tissues may act as a prognostic marker of head and neck cancer, thus deserves further investigations.