Thyroid cancer, a common type of endocrine system cancer, has witnessed rising incidence and deaths over the past few years. The role of microRNAs is being increasingly discovered in a variety of cancers, including thyroid cancer. miR-4319 has been elucidated in several studies to exert an antitumor function in multiple cancers but has never been explored in thyroid cancer. Our study proposed to explore the function and modulatory mechanism of miR-4319 in thyroid cancer. First, we confirmed the downregulation of miR-4319 in thyroid cancer tissues and cells, and revealed the correlation of miR-4319 expression and clinical features in thyroid cancer. Functional assays illustrated that miR-4319 attenuated proliferation, migration, and epithelial-to-mesenchymal transition (EMT) in thyroid cancer. Mechanistically, we identified through the miRDB database and proved that miR-4319 targeted SMAD specific E3 ubiquitin protein ligase 1 (SMURF1). Furthermore, we discovered that miR-4319 competed with fused in sarcoma (FUS) to bind to SMURF1, inhibiting the stabilization of SMURF1 messenger RNA. Rescue assays suggested that miR-4319 retarded proliferation, migration, and EMT through SMURF1. Collectively, the results of this study showed that miR-4319 inhibited the development of thyroid cancer by modulating FUS-stabilized SMURF1, indicating miR-4319 as a potent biological target for thyroid cancer. © 2019 Wiley Periodicals, Inc.