Objective To evaluate the expression of reactive oxygen species (ROS), glutataione (GSH), total superoxide dismutase (T-SOD), total antioxidation capacity (T-AOC), thioredoxin reductase (TrxR) under the intervention of hedysarum polysaccharides-1 (HPS-1) in A549 cells. Methods After treated by HPS-1 in different doses (50 mg/L, 100 mg/L, 200 mg/L, respectively), the viability of cell lines was detected by MTT method under microscope. The apoptosis of cell lines was detected by flow cytometry (FCM). The expressions of ROS, GSH, T-SOD, T-AOC, and TrxR in cell supernatant were measured by chemiluminescence method. Results Determined by MTT/FCM/ELISA, the results showed that different doses of HPS-1 could inhibit the proliferation and promote the apoptosis of A549 cells (allP<0.05). The expression levels of GSH, T-SOD, T-AOC, and TrxR were significantly decreased (allP<0.05) and the expression levels of ROS and MDA were significantly increased (allP<0.05) in a concentration-dependent manner in A549 cells treated with HPS-1, and these effects were significantly weakened in A549 cells with time extending (allP<0.05). Conclusion HPS-1 has a markedly effect on inhibiting cellular proliferation and inducing cellular apoptosis of lung adenocarcinoma A549 cells, which may be associated with the change of oxidation/antioxidant.