Preeclampsia (PE) is a condition of pregnancy in which symptoms of hypertension develop after 20 weeks of gestation. it can lead to placental dysfunction, maternal and perinatal mortality and morbidity. The incidence of PE is increasing, posing a serious threat to the lives of pregnant women and their unborn children. Currently, most of the research on the pathogenesis of PE has focused on placenta, However, maternal decidualization is the basis for placental formation and growth. Chondroitin sulfate proteoglycan 4 (CSPG4) is a transmembrane protein that plays a role in cell proliferation, invasion, and migration. However, its function during decidualization is not yet understood. In this study, we investigated the role of CSPG4 and found that its expression was significantly down-regulated in the decidual tissue of patients with severe PE compared to normal pregnant women. During artificially induced decidualization, CSPG4 expression was significantly increased. Knockdown of CSPG4 by small interfering RNA inhibited decidualization, which, in turn, inhibited the invasion of trophoblast cells. In both pseudopregnant and pregnant mice, endometrial stromal cells proliferated rapidly and Cspg4 expression increased during decidualization. Therefore, we believe that CSPG4 plays a crucial role in the process of decidualization. The defect in decidualization caused by abnormal CSPG4 expression could lead to insufficient trophoblast invasion, ultimately contributing to the occurrence of PE.