Transmembrane protein 16A (TMEM16A) is a Ca²⁺-activated Cl^- channel that is overexpressed in various malignant tumors. The gene is located in chromosome 11q13 region, and its amplification is one of the main reasons for the high expression of this protein. In addition, transcriptional regulation, epigenetic regulation and microRNAs (miRNAs) can promote TMEM16A expression in many cancer cells. TMEM16A not only activates a variety of signaling pathways that promote tumor cell proliferation, migration and invasion, but also plays an important role in inhibiting tumor cell apoptosis. Therefore, the development of anticancer drugs targeting TMEM16A is of great clinical significance. This article reviews the mechanism of TMEM16A in malignant tumors, summarizes the signaling pathways of TMEM16A in promoting tumor development, and analyzes the key role of TMEM16A as a potential biomarker in tumor development. TMEM16A inhibitors may become a new treatment for cancers with high expression of TMEM16A.