Psoriasin (S100A7) is one of the members in the S100 protein family. It was first discovered as a protein abundantly expressed in psoriatic keratinocytes. Psoriasin has been implicated in a wide range of intracellular and extracellular functions, including regulation of calcium homeostasis, cell proliferation, differentiation, apoptosis, cell invasion and motility, cytoskeleton dynamics, protein phosphorylation, regulation of transcriptional factors, immune responses, chemotaxis, inflammation and pluripotency. Altered expression of psoriasin was shown to associate with a broad range of diseases, including inflammatory and immune disorders and tumors. Many lines of evidence suggested that psoriasin exerts its distinct functions through alterations in both intracellular and extracellular pathways and results alteration in gene expression. In this review, we summarize the multiple function of psoriasin and the underlying mechanisms and discuss the potential role of psoriasin as one of the biomarkers and therapeutic targets for multiple diseases.