Abstract: The QKI protein, encoded by the Quaking gene, is an RNA binding protein with signal transducing and RNA activating functions. It plays a crucial role in embryonic development and axon myelination. It has been previously demonstrated that QKI is downregulated in various malignant neoplasms such as lung cancer, gastric cancer, and colorectal cancer and is associated with tumor invasion, metastasis, and prognosis. QKI protein can participate in tumor progression through alternative splicing, cell cycle regulation, epithelial-mesenchymal transition, and other mechanisms. Expression of the QKI protein and its biological functions are regulated by DNA methylation, gene fusion, miRNAs, post-translational modifications, and other mechanisms. Quaking, as a potential tumor suppressor gene, is expected to become a significant biomarker in tumor diagnosis and treatment. This review addresses the functions and mechanisms of QKI protein in the initiation and progression of malignant neoplasms.