Objective To explore the prenatal diagnosis of twin pregnancy with fetal chromosome abnormality. Methods The prenatal diagnostic medical records of 22,466 patients who came to our hospital for genetic consultation and underwent amniocentesis were selected from January 2014 to August 2020, and the prenatal diagnostic methods, chromosome results and pregnancy outcomes were analyzed by retrospective study. Results Among the 22466 prenatal diagnosis samples successfully cultured, 353 cases of twin pregnant women were detected, 15 cases of chromosomal abnormalitieswere detected, and the abnormal detection rate was 4.25%. Among them, there were 10 cases of trisomy 21 include mosaicism, 3 cases of sex chromosome abnormalities, 4 cases of structural abnormalities, and 1 case of marked chromosomes. Among the 338 fetuses with normal karyotypes, 40 cases of chromosome microarray analysis (CMA) were abnormal, including 2 cases of possible disease and 3 cases of unclear significance. Combining the two detection methods of CMA and karyotype, a total of 22 abnormal fetuses were detected in 353 twins, with a total abnormality rate of 6.23%.Conclusion For twin pregnancy, interventional prenatal diagnosis is an effective method for detecting fetal chromosomal abnormalities and genetic diseases. It is can effectively avoid birth defects, and has important clinical application value.