Background: NAD(P)H: quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase that is involved in protection of cells against redox cycling, oxidative stress, and neoplasia. and can also bioactivate certain antitumor quinones. Many antioxidants are cancer chemopreventive agents, and tumour hypoxia are now being exploited in cancer treatment which shows considerable promise to overcome the resistance to cancer chemotherapy. Antioxidant response element (ARE) is sensitive to perturbations of cellular redox states. Our previous studies have shown that β-tyrosol (β-TY), as a phenolic antioxidant, can protects cells against DNA damage resulting from toxic H2O2. Aim: We take the present study with the goal of whether antioxidants such as β-tyrosol, butylated hydroxyanisole(BHA) and β-Naphthooflavone(β-NF) and hypoxia (pO2 0.1% -0.5%) can induce gene expression of NQO1, inhibit proliferation of human hepatoma cells SMMC-7721 and the relationship between them; whether ARE can mediate gene expression in response to antioxidans and hypoxia. Methods: SMMC-7721 human hepatoma cells are planted in plates, grown for 24h. and exposed to antioxidants and hypoxia, each alone or in combination for another 24h. The enzyme activity was determinied by spectrophotometric assay using direct measurement of NQO1 from cells cultured in Microtiter wells. Semi-quantitative reverse transcription-PCR (RT-PCR) technique was used to measure NQO1 mRNA levets. Proliferation was estimated using the crystal violet staining technique. Electrophoretic mobility shift assay (EMSA) was employed to assess protein binding to the ARE under all of These conditions. Hypoxia cells were harvested in an anaerobic chamber at the end of the incubation period. Results: Antioxidant (90ug/ml β-TY、60μmol/L BHA、80μmol/L β-NF) potently induce an increase in the activity of NQO1. From 60μg/ml to 90μg/ml, β-TY caused NQO1 activity enhancement in a dose-dependent manner The NQO1 activity induced by 80μg/ml β-TY was approximately equal to that induced by 80μmol/L β-NF; β-TY also caused NQO1 mRNA expression enhancement in a dose-dependent manner(r=0.824, P