Abstract: Objective To explore the effect of CD81 on trophoblast adhesion and related mechanisms, in order to determine the role of CD81 in the pathogenesis of preeclampsia.Methods A human first-trimester-derived trophoblast cell line (HTR-8/SVneo cells) was cultivated in vitro before transfection with adenovirus Ad-CD81 which highly expressed CD81 or si-CD81 which inhibited endogenous CD81 through interference RNA. Then, the ability of cell adhesion was detected by adhesion assay. The expression of focal adhesion kinase (FAK) in HTR-8/SVneo cells was detected by Western blot. Results Compared with Ad-CTL-infected cells, Ad-CD81- infected HTR-8/SVneo cells showed enhanced adhesion ability and increased optical density at 570 nm (P<0.05). Compared with si-CTL-transfected cells, si-CTL-transfected HTR-8/SVneo cells presented weakened adhesion ability and decreased optical density at 570 nm (P<0.05). Furthermore, with the increase of concentration gradients, the expression of FAK was down-regulated in the Ad-CD81-infected HTR-8/SVneo cells, but up-regulated in the si-CD81-transfected cells(P<0.05 or P<0.01).Conclusions CD81 can enhance the adhesion of trophoblasts, which may be associated with its inhibitory effect on FAK expression in trophoblasts.