〔Abstract〕 Objective To explore the application value of ultrasound combined with serological index detection in the screening of fetal chromosomal abnormalities in the first trimester of fetal chromosomal abnormalities. Methods A retrospective analysis of 2125 singleton pregnant women who underwent maternity check-ups at the First People's Hospital of Zhaoqing from January 2018 to June 2020. All pregnant women underwent NT ultrasound examination and serological test (free β-human chorionic membrane). Gonadotropin (fβ-HCG), pregnancy-associated protein-A (PAPPA)], with follow-up results as the gold standard, and retrospective analysis of the screening results. Results The pregnancy outcome or induction of pregnant women showed that among the 2125 fetuses, 11 had chromosomal abnormalities, and the incidence of fetal chromosomal abnormalities was 0.52%. Among them, there were 2 cases of trisomy 18, 6 cases of trisomy 21, and trisomy 13 There were 1 case, 1 case of 45X chromosome abnormality, and 1 case of chromosome fragment abnormality. Among them, NT ultrasound showed 9 cases of fetal chromosome abnormality, serological index test showed 6 cases of fetal chromosome abnormality, and combined examination showed 11 cases of fetal chromosome abnormality. The sensitivity and positive predictive value of the combined inspection were higher than the two inspection methods alone, and the difference was statistically significant (P < 0.05). Conclusion NT ultrasonography combined with serological index detection has high diagnostic efficiency in the screening of fetal chromosomal abnormalities in the first trimester, which is beneficial to prenatal and postnatal care.