Annexin A2 (ANXA2) is a multifunctional calcium-dependent phospholipid-binding protein. Previous rEPORts have shown that ANXA2 is closely related to the occurrence and development of various tumors. However, knockdown, knockout or overexpression of ANXA2 using gene regulation technologies have indicated that ANXA2 is multifunction and involved in various pathological processes including cells proliferation, tumor cell invasion, neoangiogenesis, the plasmin system, inflammatory response, epithelial - mesenchymal transition, anti-cancer drug resistance, and side effects. It also participates in the occurrence and development of tumors and non-tumor diseases. These pathological effects and pathways of ANXA2 at the genetic level were summarized on the basis of recent developments and we also explored whether ANXA2 can be used as a target for eaR_Ly diagnosis and treatment of the related diseases.