Identifying the pathogenesis, timely diagnosis and adequate treatment of pre-eclampsia (PE) will reduce maternal and perinatal morbidity and mortality. Objective. To analyze the hypothesis about the influence of placental terminal villus proteins on the development of PE. Patients and methods. After clinical examination and diagnosis, six patients were included in the study: three with normal pregnancy and three with severe PE. The age of patients ranged from 19 to 32 years, and their gestational age ranged from 34 to 40 weeks. All patients were Caucasian and lived in normal conditions in Moscow. After delivery, samples were taken from the middle layer of the placenta, mainly with the terminal villi. Placental terminal villus proteins were determined using panoramic mass spectrometry. Results. A total of 1,858 common proteins were recorded in PE and normal pregnancy. In addition, 532 (28.6%) and 301 (16.2%) different proteins were found in normal pregnancy and PE, respectively. In the group of common proteins, 76 cases were identified in which proteins in three various measurements could differ in NSAF by 2–3 times, 39 by 3–4 times, and 51 by more than 4 times. After excluding random cases, only 10 highly expressed proteins remained: CSPG2, CFAH, NOS3, XPO1, PARP1, PRG2, K1C9, K1C10, NHRF1, and ITA2B. When determining protein-protein interactions (PPIs) associated with the “development of anatomical structures” (GO:0048856) of proteins identified in the placental terminal villi in PE, the ACTB protein was most actively involved. Conclusion. Candidate proteins were identified that could potentially be used to predict PE, determine its pathogenesis and possible methods for timely prevention, diagnosis and treatment. © 2025, Dynasty Publishing House. All rights reserved.