Objective To explore and analyze the application effect of comprehensive nursing in Down''s screening of pregnant women. Methods 4659 pregnant women screened by birth in Zoucheng People''s Hospital from March 2020 to March 2022 were randomly divided into two groups: 2329 control pregnant women and 2330 pregnant women in the observation group. The control group adopted routine care, and the observation group adopted integrated care. Results After nursing, the SAS and SDS scores of pregnant women in the observation group were lower than that of the control group, P <0.05; the score was higher than that of the control group, P <0.05; (3) the total satisfaction of nursing in the observation group was higher than that of the control group, P <0.05. Conclusion Comprehensive nursing can play a significant nursing role in pregnant women in Down screening, can help pregnant women stabilize their psychological state, reduce psychological pressure, and master more comprehensive and correct prenatal nursing knowledge, which is a nursing method with high application value.