Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional coactivator involved in the differentiation of stem cell as well as the development of multiple organs. Recently, TAZ has also been identified as a major component of the novel Hippo-LATS tumor suppressor pathway and to function as an oncogene in breast cancer. We show for the first time that TAZ is an oncogene in non-small cell lung cancer (NSCLC). Our results show that TAZ is overexpressed in NSCLC cells and that lentivirus-mediated overexpression of TAZ in HBE135 immortalized human bronchial epithelial cells causes increased cell proliferation and transformation, which can be restored back to its original levels by knockdown of TAZ. In addition, short-hairpin RNA (shRNA)-mediated knockdown of TAZ expression in NSCLC cells suppresses their proliferation and anchorage-independent growth in vitro, and tumor growth in mice in vivo, which can be reversed by re-introduction of shRNA-resistant TAZ into TAZ-knockdown NSCLC cells. These results indicate that TAZ is an oncogene and has an important role in tumorigenicity of NSCLC cells. Therefore, TAZ may present a novel target for the future diagnosis, prognosis and therapy of lung cancer.