Objective To explore the application value for fetuses with ultrasonographic soft markers by genomewide high resolution chromosomal microarray analysis (CMA) and investigate the relationship between Chromosome abnormalities and ultrasonographic soft markers. Methods 421 pregnant women with ultrasonographic soft markers without obvious structural abnormalities at the First Affiliated Hospital of AFMU(Air Force Medical University) from January 2015 to March 2018 were involved in the present study. All pregnant women performed invasive prenatal diagnosis. Microarray testing was performed using Affymetrix CytoScanTM 750k arrays and the results were analyzed according to biological information science database. The fetal development was regularly inspected. The follow-up were conducted with outcomes of pregnancy and fetal postnatal conditions. Results In 421 cases of ultrasonographic soft markers， there were 30 fetuses with pathogenic chromosome abnormalities，including 4.0% chromosome aneuploid and 3.1% pathogenic copy number variations. The detection rate of pathogenic chromosome abnormalities in multiple soft markers was 99%, and the detection rate of single soft markers was 6.2%. The difference was of statistic significance(P＜0. 05). Different soft markers varied in the degree of association with fetal pathogenic chromosomal abnormalities. The detection rate of nuchal translucency or nuchal fold thickening, choroid plexus cysts, lateral cerebral ventriculomegaly, Nasal bone absence or hypoplasia11, echogenic bowel, short femur length and single umbilical artery were 21.4% (6/28), 5.8% (2/34), 5.5% (4/74), 1% (3/27), 8.7% (2/23), 5.7% (2/35) and 3.7%(1/27). Conclusion Multiple soft markers and ultrasonographic soft marker: nasal bone absence or hypoplasia, nuchal translucency or nuchal fold thickening, lateral cerebral ventriculomegaly correlate with marked increased risk for fetal pathogenic chromosomal abnormality. CMA can identify chromosomal microdeletion/microduplication unrecognizab1e by conventional karyotyping analysis. The application of CMA could increase the detection rate of pathogenic CNVs in fetuses with soft markers, and effectively reduce the occurrence of birth defects.