Objective: To observe the application value of soft ultrasound marker prefrontal space ratio (PFSR) combined with non-invasive prenatal testing (NIPT) in screening fetal chromosomal abnormalities in early pregnancy. Methods: Eighty high-risk pregnant women who underwent amniotic fluid karyotyping in early pregnancy at the hospital from January 2020 to February 2023 were selected. All women were examined with obstetric ultrasound and NIPT. Amniocentesis chromosome testing was taken as the golden standard to compare the application value of soft ultrasound marker PFSR, NIPT and their combination in screening fetal chromosomal abnormalities early pregnancy. Results: Of the 80 pregnant women, 11 (13.75%) with chromosomal abnormalities were screened by amniotic fluid karyotyping, including 6 cases of trisomy 21, 2 cases of trisomy 18, 2 cases of trisomy 13, and 1 case of Turner syndrome. The sensitivity, specificity and accuracy of soft ultrasound marker PFSR for screening fetal chromosomal abnormalities in early pregnancy were 63.64%, 86.96%and 83.75%. The sensitivity, specificity and accuracy of NIPT were 72.73%, 88.41% and 86.25%. The sensitivity, specificity and accuracy of PFSR combined with NIPT were 90.91%, 98.55% and 97.50%. The specificity and accuracy of PFSR combined with NIPT were higher than those of single detection (P<0.05), but there was no significant difference in sensitivity among the three methods (P>0.05). Conclusion: Soft ultrasound marker PFSR combined with NIPT can improve the screening of fetal chromosomal abnormalities in early pregnancy, with high specificity and accuracy.