The tumor microenvironment is considered one of the main players in tumor development and progression. The tumor microenvironment composed of a large number of extracellular matrix proteins is very complex. The continuous accumulation of extracellular matrix proteins has been shown to play a key role in tumor bioregulation, including proliferation, invasion, matrix remodeling. If these processes can be detected early, and effective interventions can be given in time, the progression of the tumor may be delayed. Therefore, there is an urgent need to explore new biomarkers and therapeutic targets. In recent years, studies have shown that periostin (POSTN) may regulate multiple biological behaviors of tumor cells. Here we review the updated progress on the role of POSTN in pathologic pathways of tumor development and progression to explore whether POSTN is a potential therapeutic target.