The sodium iodine symporter (NIS) is widely distributed in various organs of the human body and serves as the structural and functional basis for the transport of iodide (I- ) in these organs. NIS is primarily expressed on the basolateral membrane of cells, providing the required I- for various life activities. It is known that the regulatory mechanism of NIS involves the actions of hormones, cytokines, transcription factors, and signaling molecules. In addition, NIS is gaining attention as an important therapeutic target for thyroid cancer, although complications arising from the absorption of radioactive iodine by other organs, such as salivary glands, during the treatment process also deserve attention. In this article, we focus on the research progress on the expression, role, and regulatory mechanism of NIS, aiming to provide new insights for clinical intervention targeting disease processes associated with NIS abnormalities.