Pulmonary arterial hypertension (PAH) is a disease characterized by a progressive increase in pulmonary vascular resistance and obliterative pulmonary vascular remodeling; however, the pathogenesis of the disease is not completely understood. Sirtuin 1 (SIRT1) is a histone deacetylase involved in cell survival and metabolism. The present study explored the potential role of SIRT1 in human pulmonary arterial endothelial cells (HPAECs) under hypoxic conditions. In vitro HPAECs were cultured and exposed to hypoxic conditions. Subsequently, SIRT1 expression levels were measured via western blotting, the generation of reactive oxygen species (ROS) was evaluated, and the interaction between SIRT1 and Akt was assessed via reverse transcription-quantitative PCR and western blotting. In addition, the effects of SIRT1 on cell proliferation and apoptosis were also investigated. The results indicated that hypoxia induced SIRT1 expression in pulmonary arterial endothelial cells, which may be associated with ROS generation. SIRT1 expression activated the Akt signaling pathway, which increased the expression levels of Bcl-2 and hypoxia-inducible factor-1 in HPAECs. Moreover, SIRT1 promoted HPAEC proliferation and inhibited HPAEC apoptosis. ROS generation enhanced the SIRT1/Akt axis, which was essential for epithelial cell injury under hypoxic conditions. Therefore, blocking SIRT1 may reduce hypoxia-induced pathological damage in HPAECs.