Down’s syndrome is an autosomal disease and its prenatal screening is particularly important. In recent years, clinical application of serological screening markers has been widely used, which improved the detection rate of Down’s syndrome, but still remained at about 60%. The new generation of sequencing technology for direct analysis of nucleic acids, which can be used for fetal chromosomal aneuploidy detection, can detect Down’s syndrome more accurately. In this paper, we compared the prenatal screening methods for Down’s syndrome in recent decades, and reviewed the new screening markers based on proteomics and bioinformatics technology for clinical application.