Annexin A2 (AnxA2) is a multifunctional protein and has complex functions regulated by post-translational modifications. Protein phosphorylation is the most popular post-translational modification of AnxA2. Ser11, Ser25 and Tyr23 are the three most important phosphorylation sites. The possible impact of phosphorylation of AnxA2 function regulation has always been a hot topic. Recently, AnxA2 has been found in the exosomes of tumor cells, and the research of AnxA2 and its phosphorylation has been expanded from intracellular to extracellular. Remarkable achievements in the study of AnxA2 and its phosphorylation have been made in many clinical disciplines. This paper reviewed the advances on the impact of phosphorylation of Ser11, Ser25, Tyr23 sites on AnxA2 function regulation and the research about AnxA2 in exosomes.