Elevated RNA polymerase III-dependent gene transcription is a hallmark of transformation and tumorigenesis. Understanding the mechanisms by which this process is regulated is key to understanding what goes wrong in cancer. Maf1 was identified as a novel transcriptional repressor that can repress transcription from all three mammalian RNA polymerases. In this study we demonstarted that SUMOylation of Maf1 is important for Maf1's ability to repress RNA polymerase III-dependent transcription. Additionally, SENP1 regulates SUMO modification of Maf1 which is important for Maf1's association with RNA polymerase III. Given that SENP1, Maf1 and RNA polymerase III-dependent transcrtipion play an important role in oncogenesis, our study supports the idea that deSUMOylation of Maf1 and induction of its target genes is important for cancer development.