Objective To explore the role and potential mechanisms of all-trans retinoic acid （ATRA） on activation and oxidative stress of hepatic stellate cell （HSC）. Methods Platelet-derived growth factor （PDGF-bb, 10 ng/ml） was applied to induce the activation of HSCs, which was then treated with ATRA at a dosage of 5 μmol/L for 48 h. The effects of ATRA on HSC activation were evaluated by detecting changes in cell growth viability and phenotypic marker expression. The effects of ATRA on HSC oxidative stress were evaluated by detecting changes in intracellular reactive oxygen species （ROS）, reduced glutathione （GSH） and malondialdehyde （MDA）, and the expression of antioxidant genes. The effects of ATRA on HSC autophagic activity were evaluated by detecting changes in autophagy marker expression and autophagic flow. Results Compared with the PDGF-bb group, the cell viability was significantly reduced in ATRA-treated HSCs （P<0.01）, as well as the expression of α-SMA and Collagen I. The intracellular levels of ROS and MDA were significantly reduced in ATRA-treated HSCs （P<0.01）, whereas the GSH level was significantly increased （P<0.01）. The expression levels of antioxidant genes （NRF2, HO-1, and ATF4）, were significantly higher in ATRA-treated HSCs than those in the normal ones under PDGF-bb condition （P<0.01）. Meanwhile, the expression of autophagy markers Beclin 1 and LC3 Ⅱ/I, and signal of autophagy flow in ATRA-treated HSCs were found to be significantly reduced （P<0.01）. Conclusion ATRA significantly inhibited PDGF-bb-induced HSC activation and reduced the level of oxidative stress and autophagic activity of HSCs, which had potential applications in the prevention and treatment of liver fibrosis.