Abstract: Objective To study the role and mechanism of endoplasmic reticulum stress (ERS) in regulating the apoptosis of hypoxia-induced preeclampsia (PE) trophoblasts in vitro.Methods PE placenta and healthy placenta were collected, and then the apoptosis rate and the levels of ERS marker gene glucose regulated protein 78 (GRP78), ERS apoptosis gene C/EBP homologous protein (CHOP), phosphorylated JNK (p-JNK) and Cleaved caspase-12 were examined. The placental trophoblasts HTR8/SVneo were cultured. A PE cell model was induced by exposing to low oxygen (1% O₂) for 24 h. The cells were treated with ERS agonists. During the induction of the PE cell model,the cells were transfected with CHOP siRNA or treated with JNK inhibitor and Caspase-12 inhibitor. Cell proliferation (D value), apoptosis rate and the levels of GRP78, CHOP, p-JNK and Cleaved caspase-12 were measured.Results The apoptosis rate and the levels of GRP78, CHOP, p-JNK and Cleaved caspase-12 in PE placenta were higher than those in healthy placenta (P<0.05). Cell apoptosis rate was positively correlated with the levels of GRP78, CHOP, p-JNK, and Cleaved caspase-12. The D value of cells in the PE group and ERS agonist group were lower than those in the control group, and the apoptosis rate and the the levels of GRP78, CHOP, p-JNK and Cleaved caspase-12 were higher than those in the control group (P<0.05). Transfection of CHOP siRNA reduced CHOP expression, JNK inhibitor reduced p-JNK expression, and Caspase-12 inhibitor reduced Cleaved caspase-12 expression in the hypoxia-induced PE model, leading to increased D value, reduced apoptosis rate, and lowered GRP78 expression (P<0.05).Conclusions ERS mediates cell apoptosis through CHOP, JNK, and Caspase-12 in the hypoxia-induced PE trophoblast model.