Objective To study the application of prenatal ultrasound monitoring in fetal cardiothoracic ratio in severe α-thalassemia. Methods The ultrasound imaging results of 42 severe α-thalassemia fetuses and 125 non-severe α-thalassemia fetuses diagnosed in our hospital from January 2017 to December 2019 were retrospectively analyzed. All the pregnant women were regularly monitored for the fetal cardiothoracic ratio by prenatal ultrasound. The fetal heart diameter (HL) and chest diameter (TL) were observed, and the cardiothoracic ratio was calculated (CR). The results of the two groups were compared. Results During 12-17 weeks, 18-22 weeks and 23-25 weeks, the HL values of the severe group were (15.43±1.83) mm, (22.46±1.92) mm and (28.71±4.34) mm respectively, which were higher than those of the non-severe group: (11.64±1.37) mm, (17.31±1.85) mm and (26.42±2.13) mm respectively (all P<0.05); during 12-17 weeks, 18-22 weeks and 23-25 weeks, the TL values of the severe group were (18.42±1.73) mm, (28.42±2.31) mm and (45.34±4.76) mm respectively, which were lower than those of the non-severe group: (23.72±2.13) mm (31.46±2.85) mm and (50.42±5.38) mm respectively (all P<0.05); during 12-17 weeks, 18-22 weeks and 23-25 weeks, the CR values of the severe group were (0.55±0.03) mm, (0.59±0.06) mm and 0.65±0.07) mm respectively, which were higher than those of the non-severe group: (0.46±0.05) mm, (0.53±0.04) mm and 0.57±0.03) mm respectively (P<0.05). During 23-25 weeks, the values of HL, TL and CR in the two groups were greater than those during 12-17 weeks, and 18-22 weeks (P<0.05). The ROC curve showed that during 18-22 weeks the CR value had the best predictive efficacy for the diagnosis of severe α-thalassemia fetuses, and its response curve area was 0.962 (95%CI: 0.931-0.965), the best threshold was 0.465 mm, the sensitivity was 95.20%, the specificity was 85.30%, and the Yoden index was 0.805. Conclusion The prenatal ultrasound monitoring of fetal cardiothoracic ratio in severe α-thalassemia fetal monitoring has a high value, and the method is safe and accurate. So it is worthy of clinical application.