Different types of tumors often present an overexpression of cyclooxygenase-2. The aim of this study was to evaluate the effects of parecoxib (NSAID, cyclooxygenase-2 selective inhibitor) in the behavior of the human osteosarcoma MG-63 cell line, concerning several biological features. Cells were exposed to several concentrations of parecoxib for 48 hours. Cell viability/proliferation, cyclooxygenase-2 expression, morphologic alterations, membrane integrity, cell cycle evaluation, cell death and genotoxicity were evaluated. When compared with untreated cells, parecoxib led to a marked decrease in cell viability/proliferation, in COX-2 expression and changes in cell morphology, in a concentration-dependent manner. Cell recuperation was observed after incubation with drug-free medium. Parecoxib exposure increased lactate dehydrogenase release, an arrest of the cell cycle at S-phase and G2/M-phase, as well as growth of the sub-G0/G1-fraction and increased DNA damage. Parecoxib led to a slight increase of necrosis regulated cell death in treated cells, and an increase of autophagic vacuoles, in a concentration-dependent manner. In this study, parecoxib showed antitumor effects in the MG-63 human osteosarcoma cells. The potential mechanism was inhibiting cell proliferation and promoting necrosis. These results further suggested that parecoxib might be a potential candidate for in-vivo studies.