Genetic association links DIORA1 to numerous autoimmune rheumatic diseases including systemic lupus erythematous, Sjögren's disease, myositis, scleroderma and rheumatoid arthritis, but its cellular function remains unknown. Here, we identify the MRCK kinase family as DIORA1 interactors. MRCK kinases regulate the activity of actin-myosin networks, including cell adhesion, motility and invasion. Mapping the interaction between DIORA1 and MRCKs, we found that DIORA1 binds three distinct modules of MRCK kinases, including the conserved autoinhibitory kinase inhibitory motif (KIM) and C1-PH-CNH domains. Knockdown of DIORA1 altered cellular phosphorylation patterns, including reduced phosphorylation of known MRCK targets. Functional analyses revealed enhanced cellular migration and invasion following knockdown of DIORA1, and RNA-sequencing and proteomic analyses confirmed upregulation of epithelial mesenchymal transition genes and proteins. In summary, our findings identify autoimmunity-associated DIORA1 as a previously uncharacterized interactor of MRCK kinases and a modulator of cell motility.