Background: Normal tissue toxicity continues to remain as a major challenge for radiation oncologists for delivering the total dose to the tumour cells in cancer patients. Cellular, molecular and plasma based early biomarkers to predict the overreactions and non-overreactions of normal tissue toxicity before the initiation of radiotherapy can be valuable for personalised treatment. The aim of the current study was to analyse the interrelationship between polymorphisms in Glutathione S- Transferases (GSTs) and Transforming Growth Factor-β1 (TGF-ß1), the plasma level/activity of these proteins with the development of chemo-radiotherapy induced oral mucositis and skin reaction in head and neck cancer (HNC) patients. Materials and Methods: We analysed polymorphisms in TGF-β1 and GST by restriction digestion of the PCR amplified products and we also assessed circulating TGF-β1 levels and GST activity by Enzyme Linked Immunosorbent Assay (ELISA). Results: The results indicate that pre-radiotherapy plasma TGF-β1 levels and total GST activity has no correlation with radiation induced normal tissue skin reaction and oral mucositis in HNC patients. Conclusion: The selected polymorphisms in TGF-β1 and GST had no influence on TGF-β1 levels and total GST activity. Plasma TGF-β1 and GST activity was not affected by the presence of selected polymorphisms and lacks significance in predicting skin reaction and oral mucositis prior to chemo-radiotherapy.