Abstract: The activation of the proto- oncogene STAT 3 is strongly controlled under physiological conditions. However, obtained evi -dence revealed that STAT3 is persistently activated in cancer cells and contributes to cancer initiation and progression. Studies demon -strated the various functions of activated STAT 3 in promoting cancer development and aggravation, including cancer cell proliferation, invasion and metastasis, drug resistance, epithelial- mesenchymal transition, regulation of the tumor microenvironment, and promo -tion of the self-renewal and differentiation of cancer stem cells. Canonically, STAT3 is regulated by signaling pathways mediated by cy -tokines and growth factors. Many studies determined that STAT 3 was also regulated by G protein-coupled receptors, cadherin engage -ment, Toll- like receptors, microRNA, and acetylation. We summarized the recent developments in the research on the regulation of STAT 3 activation.