The aim of this study was to explore the inhibitory mechanism of solid-state fermented Chinese alcoholic beverage Luzhou-flavor baijiu(NX) and Maotai-flavor baijiu(JX) on the cell proliferation of hepatoma cell line HepG2. CCK-8 (Cell Counting Kit 8) method was used to evaluate the cell proliferation of HepG2. The activity of alcohol dehydrogenase (ADH)， catalase (CAT)， xanthine oxidase (XOD) and the contents of reactive oxygen species (ROS) and nitric oxide (NO) were detected by kit to evaluate the oxidative stress response. The gene expression level of Nuclear factor erythroid 2-related factor 2(NRF2) and NAD(P)H quinone oxidoreductase 1(NQO1) was measured by real-time quantitative PCR (qRT-PCR). Results: Compared with 100 mmol/L ethanol， NX and JX significantly inhibited HepG2 proliferation. JX (6.25-100 mmol/L) had a higher promoting effect than NX on regulation of the XOD and CAT. However， NX (6.25-100 mmol/L) significantly enhanced the production of NO than JX. Both NX and JX(100 mmol/L) decreased the gene expression of NRF2 and NQO1 in HepG2. Treatment with the antioxidant N-acetylcysteine (NAC) abolished the inhibition of cell proliferation and the down-regulation of NRF2 and NQO1 induced by both JX and NX. Conclusion: Both Luzhou-flavor and Maotai-flavor baijiu may inhibit the proliferation of hepatoma cell line HepG2 through oxidative stress.