This study aimed to identify the expression profile of mRNAs and analyze the associated pathways in hypoxia-induced trophoblast cells to understand the effect of hypoxia on the pathophysiology of preeclampsia (PE). We downloaded two gene expression datasets (GSE47187 and GSE60432) from the Gene Expression Omnibus (GEO) datasets to identify altered transcriptomes. GEO2R, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks were used to reveal the functional roles and regulatory networks of the differentially expressed genes (DEGs). In total, 224 DEGs (91 upregulated and 133 downregulated) were identified, and the "HIF-1 signaling pathway" was activated in placentas from patients with PE. We validated the expression levels of five proteins in the plasma of NP and PE patients during early or late pregnancy using western blotting. In primary trophoblast cells cultured under hypoxic conditions, 754 DEGs were identified, including 362 upregulated and 392 downregulated genes. These DEGs were associated with the "HIF-1signaling pathway," "response to hypoxia," and several glucose metabolism pathways. In addition, a PPI network was constructed, and an important module, including 18 hub genes, was identified. Finally, we validated 18 hub genes using qRT-PCR. Furthermore, we performed microarray profiling of hypoxia-treated HTR8/SVneo cells (immortalized human first-trimester extravillous trophoblast cells) to validate the DEGs and pathways identified in hypoxia-induced primary trophoblast cells. Our results stress the differential expression profiles of mRNAs in hypoxia-induced trophoblast cells, which provide potential pathophysiological mechanisms for preeclampsia.