Objective:This study aimed to investigate the expression of Homeobox A1 (HOXA1) protein in placentas from pregnant women with preeclampsia using immunohistochemical techniques and to evaluate the potential role and interactors of HOXA1 in preeclampsia prognosis in silico.Methods:Placenta samples taken from 40 healthy normotensive (control) and 40 preeclamptic pregnant women were used in the study. Samples were fixed in zinc formalin and embedded in paraffin. Demographic data of the patients were recorded. Sections from paraffin blocks were examined with Hematoxylin-Eosin and HOXA1 immunostaining methods. The HOXA1 protein-protein interaction network was constructed using STRING and imported into Cytoscape. Common proteins in the networks were identified and their relationships were examined. Protein class analysis was performed with PANTHER and gene ontology (GO) analysis was performed with ShinyGO.Results:Compared to control group, placentas of pregnant women diagnosed with preeclampsia showed increased chorionic villus degeneration (0.35±0.49 vs 2.75±0.44), dilation of vessels (0.30±0.47 vs 2.10±0.72), number of syncytial knots (0.35±0.49 vs 1.85±0.59), fibrin accumulation (0.45±0.51 vs 2.75±0.44) and hemorrhagel. HOXA1 expression significantly decreased in the preeclampsia (%34.93) group compared to control group (%28.17) (p=0.0008). From network analysis, five common protein interactors (CTNNB1, MYC, ESR1, GATA3, and JUN) were identified to be involved in the co-regulation of HOXA1-related preeclampsia pathways. Many of these targets serve as gene-specific transcriptional regulators that significantly influence transcriptional processes, cellular differentiation, chromatin organization, and immune response.Conclusion:The downregulation of HOXA1 in preeclamptic placentas, combined with bioinformatic analyses, suggests potential mechanisms through which HOXA1-related pathways may influence preeclampsia pathogenesis.