Peroxisome proliferator-activated receptor-gamma (PPARgamma) and retinoic acid X-receptor (RXR) heterodimer, which regulates cell growth and differentiation, represses the TGFbeta1 gene that encodes for the protein involved in cancer biology. This review will introduce the novel mechanism associated with the inhibition of the TGFbeta1 gene by PPARgamma activation, which regulates the dephosphorylation of Zf9 transcription factor. Pharmacological manipulation of TGFbeta1 by PPARgamma activators can be applied for treating TGFbeta1-induced pathophysiologic disorders such as cancer metastasis and fibrosis. In this article, we will discuss the opposing effects of TGFbeta on tumor growth and metastasis, and address the signaling pathways regulated by PPARgamma for tumor progression and suppression.