Our investigations establish linear correlations between the ionization potential of exogenous phenol (P) and fl avone (F) derivatives and their biological eff ects on induction of a powerful cancer-protective enzyme NAD(P)H:quinone reductase (NQO1) via the Nrf2-Keap1 pathway. Th ey also show that the NQO1 activation involves (i) oxidation of the P and F inducers to oxidant species which are their quinone derivatives (Q) and (ii) oxidation by these quinones Q of two highly reactive thiol groups of a protein Keap1 activating transcription factor Nrf2. Th e linear correlations observed for benefi cial cancerprotective pathways triggered by electrophiles Q in vitro explain the linear correlations which we observe in vivo (rodents) for the inhibition of chemically-induced carcinogenesis by P and F derivatives. Our in silico evaluation of biological activity of P and F derivatives should orient the rational design of new congeners with greater potency for cancer chemoprotection and might reduce the expensive use of in vivo and in vitro bioassays.