Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), contribute to cancer progression, in particular metastasis. This process is facilitated by widespread changes in alternative splicing regulated by several RNA binding proteins. We identified Quaking (QKI) as a key regulator of alternative splicing in EMT model systems and cancer cell lines. In addition, QKI is directly repressed by epithelial microRNAs including members of the miR-200 family. Experimentally, we found that ectopic re-expression of miR-200 or knockdown of QKI was sufficient to alter the splicing patterns of numerous genes involved in cytoskeletal organisation including ADD3, DEPDC1, MPRIP, and CLSTN1.These splicing changes also correlated with QKI expression in a panel of breast cancer lines and clinical samples from the Cancer Genome Atlas data. Together, these data implicate QKI as an important regulator of widespread alternative splicing changes during EMT and cancer progression.