Preeclampsia (PE) is a pregnancy-specific disorder that is the main cause of maternal and perinatal morbidity and mortality worldwide. Inadequate trophoblastic invasion and endothelial dysfunction in the placenta are considered the foundation of the pathogenesis of preeclampsia in which soluble endoglin (sEng) plays an antiangiogenic role in the development of PE. The leukemia inhibitory factor receptor (LIFR) has been widely studied and is highly involved in arterial injury in vivo and in the migration of cancer cells in vitro. Here, we tested the hypothesis that LIFR may be correlated with preeclampsia through its regulation of the release of sEng. Our data showed that LIFR protein, the expression of which significantly decreased with the progression of pregnancy, was located in the syncytiotrophoblast and cytotrophoblast. The LIFR protein level was increased in pregnancies with preeclampsia compared with normotensive full-term pregnancies. After the overexpression of LIFR in HTR8/SVneo cells, the release of sEng as well as the migration and invasion were significantly enhanced. Moreover, we also observed that LIFR induced the expression of matrix metalloproteinase14 (MMP14) and that the knockdown or inhibition of MMP14 decreased the release of sEng, as well as increased the LIFR-induced migration and invasion of HTR8/SVneo cells. These studies demonstrated that LIFR promoted the release of sEng through MMP14 in vitro, which indicates that LIFR may be involved in the development of preeclampsia.