Signal transducers and activators of transcription (STAT) are proteins that play important roles in both signal transduction and transcription. The STAT family has seven members, i.e. STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6. Among them, STAT3 plays important roles in various pathophysiological processes such as incidence, development and metastasis of cancers, inflammation responses, and ischemia/reperfusion injury. In particular, constant abnormal activation of STAT3 is closely relevant to tumor growth and metastasis. So the inhibition of over activation of STAT3 is an important method for cancer treatment. At present, STAT3targeted inhibitors can generally be classified into two categories, i.e. peptide and peptidomimetics, and small molecular nonpeptide inhibitors. Most STAT3 inhibitors for cancer prevention are small molecular nonpeptide inhibitors. This paper reviews reported research progresses of STAT3 small molecule nonpeptide inhibitors.