ADAMs are members of the metzincin family of zinc-dependent metalloproteinases, which play a key role in the proteolytic degradation of the extracellular matrix to invade cells. It is well known that ADAMs are involved in regulating the invasion of trophoblast cells. But the function and underlying mechanism of ADAM7 in trophoblast cells is still unknown. ADAM7 knockdown strongly inhibited HTR-8 and B6Tert-1 cells proliferation, migration and invasion, while ADAM7 overexpression reversed. The expression of protein pro-caspase 3 and pro-caspase 9 was not affected by either ADAM7 knockdown or overexpression in HTR-8 and B6Tert-1 cells, while the expression of active-caspase 3 and active-caspase 9 was strongly increased in ADAM7 silenced cells and significant decreased in ADAM7 overexpressed cells. We also found that the phosphorylation of p38MAPK was significantly inhibited in ADAM7 silenced cells while it was significantly induced in ADAM7 overexpressed cells. Metformin HCl could reverse the inhibitory effects of ADAM7 knockdown on the p38MAPK signaling pathway and the proliferation of HTR-8 and B6Tert-1 cells. ADAM7 plays a positive role in trophoblast cells, which may be attributed to regulation of the p38MAPK signaling pathway. SIGNIFICANCE: It is necessary to further study the molecular mechanism of trophoblast cells proliferation, migration and invasion, and develop a more effective treatment to preeclampsia. This research might provide a new target for further research in this area.