Objective:To investigate the effect of equol on the proliferation of colom cancer cells and to explore the mechanisms.Methods: Colon cancer cells (DLD1,HCT15,COLO205,LOVO,SW480) were incubated, the cell proliferation was identified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay.Reverse transcription PCR and Western blot were used to measure the mRNA and the protein expression of estrogen receptor and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)in the colon cancer cells, respectively.Moreover, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay was used to investigate the effect of estrogen receptor(ER) inhibitor,ERα agonist, and estrogen receptor ERβagonist on the cell proliferation.Results: ERα was faintly expressed in the DLD-1 and HCT-15 cells.However, ERβ expression in DLD1, HCT15, COLO205, LOVO, and SW480 colon cancer cells.Different concentrations of equol (0, 0.5, 1, 5, 10 μmol/L) significantly inhibited the growth of HCT-15 cell with the expression of ERα and ERβ.More-over, different concentrations of equol (0, 0.5, 1, 5, 10 μmol/L) significantly inhibited the growth of LOVO, and SW480 cells with the ERβ expression in a dose-dependent manner as demonstrated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assay.mRNA expressions of ERα and ERβ in HCT-15 were stimulated significantly.Western blotting proved that the protein expressions of ERα and ERβ increased with the increasing of equol dose.Moreover we found significant difference of Nrf2 protein expression in HCT-15 cell stimulated by different concentrationss of equol.After the similation of estrogen receptor inhibitor, ERα agonist, or ERβ agonist, we found that only dif-ferent concentrations of ERβ agonist(0, 1, 10, 100, 1 000, 10 000 nmol/L) significantly inhibited the growth of HCT-15, LOVO, and SW480 in adose-dependent manner.Estrogen receptor inhibitor and ERα agonistdid not present significant effect on the cell proliferation of HCT-15, LOVO, and SW480.Conclusion: Equol inhibited the colon cancer cell proliferation by its estrogenic activities and antioxidant activities.