Genetic alterations such as mutations (gain of function mutations of NRF2 and loss of function mutations in KEAP1 and CUL3), and copy-number changes (amplification of NRF2 and deletion of KEAP1 and CUL3) leads to oncogenesis and drug- and radio-resistance in different types of cancers including HNSCC [8, 9]. Here, NFE2L2 is linked to head and neck squamous cell carcinoma.