Objective：To investigate the screening and preliminary validation of potential key genes for the regulation of BeWo cell fusion based on bioinformatics，since syncytiotrophoblasts（STBs） are a type of multinucleated epithelial cells located at the outermost layer of the placenta and are generated by the differentiation and fusion of cytotrophoblasts（CTBs）. STBs play an important role in the secretion of key hormones for pregnancy maintenance and nutrition exchange between mother and fetus during pregnancy. However，the regulatory mechanism of placenta trophoblast cell fusion remains unclear. Methods：The microarray datasets of BeWo cells before and after cell fusion were searched and downloaded from GEO database. A bioinformatics analysis was performed for a comprehensive analysis of all datasets to screen out the differentially expressed genes（DEGs），and then a cluster analysis was performed based on GO and KEGG. The PPI network was used to screen out node genes，and qRT-PCR was used to verify the differential expression of can－didate genes before and after cell fusion. Results：A total of 137 differentially expressed genes were screened out from two datasets，among which 25 were shared by the two datasets and were involved in cell migration，cell adhesion，hormone metabolism，and the MAPK signaling pathway. Three candidate genes were screened out by the PPI network and validated by qRT-PCR，and the results were consistent with the information analysis. Conclusion：This study provides some potential target genes for the research on trophoblast fusion and gives a clue to molecular regulation mechanism.