Abstract: Objective: To investigate the protective effect of aloe polysaccharide on oxidative damage in HepG2 cells, and analyze its antioxidant capacity in vitro. Methods: HepG2 cells were used as the study target, to establish D-galactose-induced cell oxidation damage model and pre-protected with different concentrations of aloe polysaccharide. Cell Counting Kit-8 was used to determine the survival rate of HepG2 cells, biochemical assays were performed to detect the cellular superoxide dismutase, catalase and glutathione peroxidase activities, enzyme-linked immunosorbent assay was used to determine the total antioxidant capacity and malondialdehyde content. Quantitative real-time PCR was used to detect the cellular Keap1, Nrf2, NQO1 and HO-1 gene expression levels. Results: Compared with the D-galactose model group, the pre-protection with 25, 50, 100 μg/mL of aloe polysaccharide increased the survival rate of HepG2 cells to different degrees. Aloe polysaccharide significantly enhanced the activity of antioxidant enzymes in cells and reduced the production of malondialdehyde in cells (P<0.05), and the effect was proportional to the concentration of aloe polysaccharide. The expression of Keap1 in cells was significantly reduced, and the expression of Nrf2, NQO1 and HO-1 in cells was significantly increased (P<0.05). Conclusion: Aloe polysaccharide can reduce oxidative stress damage in HepG2 cells, activate Nrf2 expression and inhibit its ubiquitination degradation, increase the transcription level of downstream NQO1 and HO-1, enhance the activity of cellular antioxidant enzymes and regulate the cellular redox system, to reduce the degree of oxidative damage and improve the effectiveness of cellular resistance to oxidative stress damage.