BACKGROUND: Centromere protein F (CENP-F) is an important nuclear matrix protein that regulates mitosis and the cell cycle, and plays a crucial role in recruiting spindle checkpoint proteins to maintain the accuracy of chromosome segregation. Studies have shown that CENP-F is closely involved in the pathogenesis of various diseases, particularly in the development and progression of malignant tumors, where it exhibits significant oncogenic activity. OBJECTIVE: This review aims to systematically summarize the molecular structure, subcellular localization, expression regulation, intracellular transport mechanisms, biological functions, and carcinogenic mechanisms of CENP-F, as well as explore its potential value in cancer diagnosis and therapy. METHODS: A comprehensive review and analysis of domestic and international research literature related to CENP-F were conducted, focusing on its role in tumorigenesis, development, and as a therapeutic target. RESULTS: CENP-F acts as an oncogene and can maintain or promote the malignant phenotype of tumor cells through multiple mechanisms, including regulating signaling pathways related to cell proliferation and apoptosis, promoting metabolic reprogramming, angiogenesis, and tumor cell invasion and metastasis. Additionally, it plays an important role in the immune microenvironment and drug resistance regulation. CONCLUSION: CENP-F plays a key, multidimensional role in tumor biology and is a promising therapeutic target for cancer treatment. Further exploration of the core pathways through which CENP-F regulates tumorigenesis and its potential for clinical translation is needed.