Annexins are a group of calcium- and phospholipid-dependent proteins. As a member of the annexin, annexin A2 (Anxa2) is widely distributed in nucleus, cytoplasm and extracellular surface and mainly expressed in human endothelial cells, mononuclear cells, macrophages, marrow cells and some tumor cells. Accumulated evidences indicated that Anxa2 deregulation was associated with the occurrence, invasion and metastasis of cancers. Anxa2 up-regulation was related to the development, invasion, metastasis and drug resistance of hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, acute promyelocytic leukemia and renal cell carcinoma; while Anxa2 down-regulation was associated with prostate cancer, esophageal squamous carcinoma and nasopharyngeal carcinoma and sinonasal adenocarcinoma. The association between Anxa2 and malignant tumors as well as the potential action mechanisms were summarized in current work. Anxa2 might be used as a potential biomarker for the diagnosis, treatment and prognosis of certain tumors.