Ki-1/57 is a cytoplasmic and nuclear protein, associated with serine/threonine protein kinase activity and gets phosphorylated on serine and threonine residues upon cellular activation. In recent studies we demonstrated that Ki-1/57 interacts with the Chromatin-Helicase-DNA-binding domain protein 3 (CHD3) and with the adaptor/signaling protein RACK1 in the nucleus. Using the protein arginine-methyltransferase-1 (PRMT1) as bait in the yeast two-hybrid system we identified Ki-1/57 as an interacting protein, along with 14 other proteins. Most of them are involved in RNA transcriptional regulation or RNA metabolism. Next, we found that Ki-1/57 and its putative paralogue CGI-55 have two conserved RGG/RXR-box clusters and are substrates for arginine-methylation by PRMT1. In mapping studies, we observed that all Ki-1/57 protein fragments containing the RGG/RXR-box clusters interact with PRMT1 and are targets of methylation in vitro. Furthermore we found that Ki-1/57 is a target of methylation in vivo, principally in the nuclear compartment, where PRMT1 is predominantly localized. Treatment of Hela cells with Adox and actinomycin D cause disappearance of Ki-1/57 from and translocation of CGI-55 to the cytosol. It is speculated that methylation of Ki-1/57 is essential for its localization to the cytoplasm and that it is associated with export of mRNA. Finally, our data show that Ki-1/57 and its paralogue CGI-55 are substrates for PRMT1 and present different cellular localization after inhibition of protein methylation and RNA synthesis.