Quorum sensing (QS) is a mechanism of intercellular communication that enables microbes to alter gene expression and adapt to the environment. While QS has been extensively studied in bacteria, little is known about cell-cell communication in archaea. We could show that for Haloferax volcanii, the transition from motile rods to non-motile disks is dependent on a possibly novel, secreted small molecule present in cell-free conditioned medium (CM). Moreover, we determined that this putative QS molecule fails to induce the morphology transition in mutants lacking potential regulatory factors, DdfA and CirA. Quantitative proteomics of wild-type cells demonstrated that at least 236 proteins have significant differential abundances in the presence of CM. Conversely, in the ∆ddfA mutant, addition of CM resulted in only 110 proteins of significant differential abundances. These results confirm that DdfA is involved in CM-dependent regulation. CirA, along with other proteins involved in morphology and swimming motility transitions, is among the proteins regulated by DdfA. These discoveries significantly advance our understanding of microbial communication within archaeal species. Please note that this dataset is an extension to PXD040781. The raw files included here are additional MS measurements, but the search and quantification results correspond to a combination of all MS files (incl. those from PXD040781).