The major findings in the present study were as follows: (1) compared with those in healthy pregnant women, serum levels of PSG9 in pregnant women with preeclampsia were significantly lower; (2) application of PSG9 at a concentration of 0.1 μg/mL to HUVECs increased the expression levels of Orai1 and Orai2, but not Orai3, thus promoting SOCE; (3) application of PSG9 at a concentration of 0.1 μg/mL to HUVECs increased eNOS expression levels, which enhanced the level of NO production; (4) BTP2, an inhibitor of Orais, blocked this PSG9-induced eNOS expression and NO production in HUVECs. Here, ORAI3 is linked to preeclampsia.