Abstract: Objective To investigate the changes of follistatin-like protein 1 (FSTL1) in the serum of patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and the regulatory effects of FSTL1 on the biological behavior of human umbilical vein endothelial cells (HUVECs) in an OSAHS cell model.Methods ELISA was used to detect FSTL1 levels in the serum of OSAHS patients. An OSAHS model was established through treatment of HUVECs under intermittent hypoxia (IH). FSTL1 knockdown was performed, followed by CCK-8 assay, wound healing assay, and flow cytometry to assess changes in cell viability, migration, and apoptosis. The expression of the nuclear factor κB (NF-κB) pathway in HUVECs was detected by Western blot and immunofluorescence staining.Results Serum FSTL1 levels were significantly elevated in OSAHS patients（P＜0.001）. IH-treated HUVECs showed significantly increased FSTL1 mRNA expression, decreased cell viability and migration, and enhanced apoptosis（P＜0.001）. Knockdown of FSTL1 in IH-treated HUVECs increased cell viability and migration, while reducing apoptosis（P＜0.05）. IH treatment significantly upregulated the expression of tumor necrosis factor-α (TNF-α) and Toll-like receptor 4 (TLR4) and downregulated endothelial nitric oxide synthase (eNOS) levels（P＜0.05）. FSTL1 knockdown inhibited TNF-α and TLR4 expression and increased eNOS levels（P＜0.05）. IH-treated HUVECs exhibited significantly increased phosphorylation of p65 and IκBα, whereas FSTL1 knockdown reduced their phosphorylation levels（P＜0.001）.Conclusions FSTL1 expression is significantly elevated in the serum of OSAHS patients. Knockdown of FSTL1 can inhibit NF-κB pathway activation in IH-treated HUVECs, thereby alleviating IH-induced endothelial cell injury.