The purpose of the study is to investigate the expression of epithelial sodium channel (ENaC) in normal pregnancy and severe preeclampsia placenta and to explore the underlying mechanism of the relationship between the altered ENaC expression and onset of preeclampsia. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to check epithelial sodium channel subunits expression in mRNA and protein level in first term and full term placental tissue. ENaCα specific RNAi were used to knockdown ENaC expression and cell invasion and migration assay were used to check whether reduced expression of ENaC can compromise trophoblast cell function. The result showed that ENaCα was highly expressed in first term placental trophoblast cells; while EnaCβ was highly expressed in full term placenta. Knockdown ENaCα expression by using small interfering RNA reduced the invasive and migration abilities of HTR-8/SVneo cell. Real time-PCR and Western blot analysis showed that the expression levels of ENaCβ were also significantly lower in severe preeclampsia compared with normal pregnancy. It is concluded that the ENaC played an important role in trophoblast cell invasion and migration. Reduced expression and activity of epithelial sodium channel in trophoblast cells may be involved in the pathogenesis of preeclampsia.