Abstract NONO is recognized as a critical molecular scaffold involved in both transcriptional and posttranscriptional regulation. Mutations in NONO are frequently linked to congenital heart diseases (CHDs) in humans. However, the mechanisms by which NONO regulates cardiac development remain elusive. Here, we identified NONO as a pivotal dual-function regulator of cardiomyocyte differentiation in human induced pluripotent stem cells (hiPSCs).