Abstract: Prenatal diagnosis is to make the diagnosis of fetal genetic diseases, structural abnormalities and pregnancy-related diseases before birth thus could provide basis for the intrauterine treatment or selectively termination of pregnancy. Proteomics-based identification of biomarkers for prenatal diagnosis in maternal plasma, amniotic fluid and reproductive fluids has made significant progress in the past few years. This is attributed mainly to advances in various technology platforms associated with mass spectrometry-based techniques. As these techniques are high through put, sensitive, and require only small quantities of body fluids, especially the discovery of biomarkers in maternal serum which has more advantages than traditional amniocentesis, chorionic villus sampling, and fetal blood sampling, and it is hoped that they will pave the way for the development of effective noninvasive approaches. By comparing the differentially expressed proteins between different clinical status, case and control, and different developmental period of certain disease, proteomic technology has been widely used in tumor biomarker studies. Up to now, many researchers all over the world applied proteomics in the discovery of prenatal diagnostic biomarkers, and found some candidate biomarkers for aneuploids, preeclampsia, intrauterine growth retardation, and some structural abnormalities. In this review we discuss the main advances in the application of proteomics in prenatal diagnosis.