Proper differentiation of trophoblast cells in the human placenta is a prerequisite for a successful pregnancy, and dysregulation of this process may lead to malignant pregnancy outcomes, such as preeclampsia. Finding specific markers for different types of trophoblast cells is essential to understand trophoblast differentiation. Here we report that placenta-specific protein 8 (PLAC8) is specifically expressed in the interstitial extravillous trophoblast cells (iEVTs) on the fetomaternal interface. Utilizing model systems including placental villi-decidua co-culture, iEVTs induction by using primary trophoblast cells or explants, etc, we found that PLAC8 promotes invasion and migration of iEVTs. Mechanistically, time-lapse imaging, GTPase activity assay, co-IP and RNA-seq studies show that PLAC8 increases the Cdc42 and Rac1 activities and further induces the formation of filopodia at the leading edge of the migratory trophoblast cells. More interestingly, PLAC8 is significantly upregulated under hypoxia and expression of PLAC8 is higher in iEVTs from preeclamptic placentas as compared to those from the normal control placentas. Together, PLAC8 is a new marker for iEVTs and play an important role in promoting trophoblast invasion and migration.