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NRF2 is a master regulator of the anti-oxidative stress response through controlling the expression of anti-oxidative stress response proteins and detoxifying enzymes. Cancer cells also exploit NRF2 protective functions to thrive and resist anti-tumor drugs. NRF2 is highly active in several types of human cancers and is associated with aggressiveness and metastasis. NRF2 affects many targets that are involved in hypoxia, angiogenesis, invasion, drug resistance, and epithelial-mesenchymal transition. NRF2 was found to be targeted by many microRNAs, so that it could be used as effective cancer therapy to improve the outcomes and contribute to the advancement of anti-tumor drugs.