Pharmacological modification of the redox properties of tumor cells is a promising approach to enhance the efficiency of antitumor therapy. Currently, the transcription factor Nrf2 is considered as a new target for the development of selective chemosensitizers. Nrf2 plays a key role in regulation of cellular redox homeostasis against stress and during adaptation processes. Many natural and synthetic phenolic antioxidants are inducers of Nrf2 transcriptional activity. Due to differences in Nrf2 transcriptional activity between normal and tumor cells, phenolic antioxidants at certain concentrations act as biological regulators the antioxidant activity of which has two different effects: in tumor cells they promote the development of oxidative stress and enhance the effect of antitumor drugs, in normal cells these antioxidants exhibit protective properties. The review discusses the possible molecular mechanisms of action and the prospects for the clinical use of natural and synthetic phenolic antioxidants in antitumor therapy.