Notch1 intracellular domain (NICD) is the transcription factor which controls cell fate and differentiation in embryonic and tumor cells. Snail has a critical role which increases invasion and metastasis of cancer cell as a transcription factor and epigenetic regulator. Recently, we discovered NICD induced Snail degradation by direct binding interaction with Snail. In this experiment, we found that Snail suppressed transcriptional activity of the protein complex formed with NICD and RBPJk in nucleus. Moreover, Snail decreased transcription of NICD target genes via competing with MAML1, co-activator, in NICD complex. In conclusion, Snail inhibited NICD-mediated transcriptional activation of target genes by physical interaction with NICD. (c) 2013 Elsevier Inc. All rights reserved.