Previous studies have revealed that microRNA (miR)-150 can act as an oncomiR or a tumor suppressor in numerous types of hematological malignancy and solid tumor. However， the function of miR-150 in papillary thyroid carcinoma (PTC) remains elusive. The present study aimed to investigate the function of miR-150 in PTC and its underlying molecular mechanism. The expression of miR-150 was identified to be significantly downregulated， whereas that of mucin (MUC)4 was significantly upregulated in PTC tissues and cell lines compared with corresponding controls. Further experiments demonstrated that MUC4 is a direct target of miR-150. PTC cell proliferation and capacity for migration and invasion decreased following miR-150 overexpression. It was also demonstrated that miR-150-mediated MUC4 downregulation was associated with an accompanying decrease in human epidermal growth factor receptor 2， as well as its phosphorylated form， resulting in suppressed activation of downstream signaling. In conclusion， the present study demonstrated that miR-150 may serve a key function in suppressing the malignant growth and aggressive behavior of PTC cells through the downregulation of MUC4. These findings may provide a novel approach for diagnostic and therapeutic strategies for PTC.