T-box genes regulate development processes, some of these genes having also a role in cell proliferation and survival. TBX15 is a T-box transcription factor that, recently, has been proposed as a marker in prostate cancer, but its function in carcinogenesis is unknown. Here the role of TBX15 in carcinogenesis was investigated using thyroid cancer cell lines. First, using western blot analysis, we show that the expression of TBX15 was altered in thyroid cancer cells lines with respect to normal thyroid cells. Transfection of thyroid cancer cells with TBX15, in the presence or absence of camptothecin as a cytotoxic agent, proved non effect of TBX15 in cell viability; but, it increased cell proliferation after 48 h of transfection (P < 0.01). Consistently, apoptosis was reduced in TBX15 transfected cells (P < 0.01) which also showed a decrease of the proapoptotic Bax regulator and an increase of the antiapoptotic Bcl2 and Bcl-XL regulators. Additionally, siRNA shutdown of constitutive TBX15 increased apoptosis. TBX15 transfection did not alter colony formation and cell migration. Taken together, these results indicate for the first time an antiapoptotic role of TBX15 in cancer cells, suggesting a contribution of TBX15 in carcinogenesis and the potential therapeutic target of TBX15.