Departmental sources Background: Preeclampsia is a severe obstetric complication affecting the health of pregnant women. The aim of this study was to determine the effect of LAMA4 gene on extravillous trophoblasts (EVTs) in the pathogenesis of preeclampsia and its possible regulatory mechanism. Material/Methods: HTR-8/SVneo cells were transfected with small-interfering ribonucleic acid (siRNA) targeting LAMA. The LAMA4 protein level was detected via Western blotting. Moreover, the influences of LAMA4 gene on the proliferation, migration and invasion of HTR-8/SVneo cells were detected via cell counting kit-8 (CCK-8) assay and Transwell assay. We also assessed the influences of LAMA4 gene on vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) messenger RNA (mRNA) levels in HTR-8/SVneo cells as measured by reverse transcription-polymerase chain reaction (RT-PCR). Results: The cell lines with downregulation of LAMA4 gene were successfully established by transfection. Compared with those in the normal group, the proliferation, migration, and invasion of HTR-8/SVneo cells declined, the VEGF mRNA level was reduced, and the sFlt-1 mRNA level was increased in the silencing group. Conclusions: Downregulation of the LAMA4 gene inhibits the proliferation, migration, and invasion of EVT to suppress the expression of vascular factors, leading to the occurrence or development of preeclampsia. Our data provide new insights into modulation of LAMA4 expression as a potential target for therapy against preeclampsia. Further research is needed on placenta sampling from pre-eclamptic pregnancies to validate the effect of LAMA4 expression compared to control pregnancies.