Abstract: Objective To investigate the effects of endogenous polypeptide PFCSH2 on the migration and invasion of injured human umbilical vein endothelial cells (HUVECs), and explore the feasibility of endogenous polypeptide in the treatment of preeclampsia. Methods HUVECs were stimulated by tumor necrosis factor-α (TNF-α) (40 μmol/L) to establish a model of vascular endothelial injury in preeclampsia. The effects of PFCSH2 on cell proliferation were detected by CCK-8 kit. The expression of related genes was detected by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). The effects of polypeptide PFCSH2 on the migration and invasion of HUVECs were analyzed by the wound healing assay, Transwell chamber invasion test and tubule formation test. Results According to RT-qPCR results, the polypeptide treatment group presented remarkable decreases in the levels of endothelin-1 (ET-1), soluble endothelial factor (sENG) and tissue plasminogen activator (TPA-1) compared with the tumor necrosis factor-α (TNF-α) group (P＜0.05). Treatment with PFCSH2 resulted in enhanced abilities in the migration and invasion of HUVECs (P＜0.05). The tubule formation test confirmed substantial increases in the number, length and branches of blood vessels in the polypeptide treatment group compared with those in the injure group (P＜0.05). Conclusions Peptide PFCSH2 can repair the injury of HUVECs caused by TNF-α in a concentration gradient-dependent manner, with the best effect at the concentration of 30 μmol/L, and can promote the migration and invasion of HUVECs. Endogenous polypeptide PFCSH2 exerts protective effects on vascular endothelial injury, which may play a role by promoting migration and invasion of HUVECs.