Objective：The present study was designed to investigate the protection of astragaloside Ⅳ（AS-Ⅳ）on human aortic endothelial cells（HAECs）after hypoxia injury and underlying mechanism. Methods：HAECs were cultured in 8% O2 to form hypoxic injury models. The cells were divided into control group（C），hypoxic group（H）and AS-IV treatment group（AS-Ⅳ，50 μg/mL）. The protective effect of AS-Ⅳ on HAECs after hypoxia was observed，and the migration，proliferation and tube formation of the cells were analyzed. Autophagy related proteins were also identified. Results：Compared with the C group，the cells with hypoxia presented increased supernatant lactic dehydrogenase（LDH）concentration（25.33 ± 1.70 U/L vs. 5.33 ± 1.25 U/L），decreased cell viability（81.12% ± 0.72% vs. 100.00% ± 3.07%），cellular migration and proliferation ability and tube formation（30.91 ± 3.78 vs. 62.1 ± 7.56）. Furthermore，the protein expression of Beclin and LC3-II of the injured cells were decreased. After AS-Ⅳ treatment，compared with the H group，decreased LDH release（18.33 ± 1.25 U/L），increased cell viability（85.71% ± 2.48%），cellular migration and proliferation ability，and tube formation（48.64 ± 4.80）were observed. And the protein expression of Beclin and LC3-II increased. Conclusion：AS-Ⅳ can alleviate hypoxia-induced damage and may promote angiogenesis of HAECs by the autophagy signaling pathway.