The purpose of this study was to investigate the mechanisms of the antitumor effect of celecoxib (CXB) in the treatment of human medullary thyroid carcinoma (MTC). Human MTC TT cells were cultured with different concentrations (0, 20, 40, 60 µmol/l) of CXB following 0-72 h in vitro. An MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to determine the growth inhibition of MTC in vitro. Flow cytometry was performed to analyze the cell cycle of TT cells. Levels of prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA) method. The expression profile of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) was measured by western blot analysis. In the present study, it was identified that CXB inhibited TT cell proliferation and induced apoptosis in a dose- and time-dependent manner. The cell cycle was arrested at G0/G1 and the percentage of cells in S phase was markedly decreased. The expression levels of PGE2 were inhibited by CXB. CXB effectively downregulated the expression of COX-2 and VEGF in a dose- and time-dependent manner. These data demonstrated that CXB inhibited the proliferation of MTC TT cells in vitro and thus may be effective as an antitumor therapy for human MTC.