The Keap1-Nrf2 pathway is a critical regulator of cellular responses to oxidative and electrophilic stress, involving the transcription factor Nrf2 and the repressor protein Keap1. Nrf2 binds to the antioxidant response element (ARE) in target genes, promoting the expression of genes involved in antioxidant and detoxification pathways. Keap1 typically degrades Nrf2 through ubiquitination, but modifications to Keap1's cysteine residues can disrupt this process, leading to Nrf2 activation and increased gene expression. In cancer cells, constitutive activation of the Keap1-Nrf2 pathway provides growth advantages by enhancing chemoresistance and promoting tumor cell proliferation. Various mechanisms, including somatic mutations, epigenetic silencing, and post-translational modifications, can lead to constitutive Nrf2 activation. Therapeutic approaches, such as Nrf2 inhibitors and cancer suicide gene therapy, aim to target this pathway to improve cancer treatment outcomes. The review highlights the importance of understanding the Keap1-Nrf2 pathway in cancer and the potential for developing targeted therapies.The Keap1-Nrf2 pathway is a critical regulator of cellular responses to oxidative and electrophilic stress, involving the transcription factor Nrf2 and the repressor protein Keap1. Nrf2 binds to the antioxidant response element (ARE) in target genes, promoting the expression of genes involved in antioxidant and detoxification pathways. Keap1 typically degrades Nrf2 through ubiquitination, but modifications to Keap1's cysteine residues can disrupt this process, leading to Nrf2 activation and increased gene expression. In cancer cells, constitutive activation of the Keap1-Nrf2 pathway provides growth advantages by enhancing chemoresistance and promoting tumor cell proliferation. Various mechanisms, including somatic mutations, epigenetic silencing, and post-translational modifications, can lead to constitutive Nrf2 activation. Therapeutic approaches, such as Nrf2 inhibitors and cancer suicide gene therapy, aim to target this pathway to improve cancer treatment outcomes. The review highlights the importance of understanding the Keap1-Nrf2 pathway in cancer and the potential for developing targeted therapies.