Human cyclin A(2) participates in cell cycle regulation, DNA replication, and transcription. Its overexpression has been implicated in the development and progression of a variety of human cancers. However, cyclin A(2) or its truncated form is very unstable in the absence of binding partner, which makes it difficult to get a deep insight of structural basis of the interactions. Therefore, biophysical studies of the full-length human cyclin A, would provide important information regarding protein stability and folding/unfolding process. To the best of our knowledge, these have not been reported. In this report, we found that cyclin A(2) stability depended on pH, salt concentration, and denaturant concentration, and low concentration denaturant increased cyclin A, stability studied by UV melting, fluorescence spectroscopy, limited proteolysis, and circular dichroism. The thermal unfolding/folding process could be described by Lumry-Eyring model: N <-> I -> D, followed by decreasing alpha-helix content and forming intermolecular antiparallel pleated beta-sheet structures in the aggregate. Our results are of importance for studying the interactions between cyclin A(2) and therapeutic agents, such as small molecules or peptides, because cyclin A(2) is very unstable in the absence of its biological associated kinases.