Objective: To investigate the clinical value of the two-dimensional ultrasound combined with four-dimensional ultrasound in the diagnosis of fetal malformation in different gestational weeks. Methods: The pregnant women with different pregnant weeks from January 2010 to November 2012 were enrolled to subject to two-dimensional ultrasound screening during early pregnancy, the second trimester and late pregnancy. Women initially suspected to have fetal malformation were underwent two-dimensional ultrasound and four-dimensional ultrasonography. The two-dimensional ultrasound examination results and the two-dimensional ultrasound examination combined with four-dimensional ultrasound results and clinical delivery results were compared and analyzed. Results: A total of 2930 fetus were labored from 2891 pregnant women, 124 congenital anomalies were detected through the clinical observation and follow-up, of which 35 genito urinary system, 31 digestive system, 23 heart, 14 pleural effusion, 8 fetal tumor, 8 skin edema, 5 limbs fracture malformation. The accuracy rate of two-dimensional ultrasound combined with four-dimensional ultrasound in the diagnosis of fetal malformation was significantly higher than that of simple two-dimensional ultrasound examination (P<0.05). Conclusion: The ultrasound for diagnosis is available for the severe fetal deformity in early pregnancy, and partly screening for fetal structural abnormalities during the second trimester, and it can increase the detection rate of late onset fetal malformation in the third trimester of pregnancy. The ultrasound examination is an important method for examination of fetal deformity, and combination of two-dimensional and four-dimensional ultrasonography can significantly improve the diagnostic rate of fetal malformation and is recognized as a preferred method for timely diagnosing the fetal abnormalities and reducing the birth defects. It is recommended that the diagnosis of fetal deformity should be based on the ultrasonic characteristics of different gestational weeks, resulting in improving the detection rate and providing reliable reference for clinical diagnosis.