Objective Hypoxia can promote stem cell proliferation and migration through HIF-1a. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-a, and ER stress, however, while little is known about HIF-a and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1a and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation.Method ADSCs were pretreated with hypoxia, HIF-1a gene transfection, and HIF-1a gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1a in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1a in ADSCs under hypoxic conditions.Result The cell proliferation and migration assay results show that hypoxia and HIF-1a overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1a inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1a and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1a pathway, thereby regulating the cellular state of ADSCs, was also observed.Conclusion Hypoxia and HIF-1a play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1a-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1a and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.