The objective of this study is to investigate the effects of aspirin and nimesulide on cell proliferation, apoptosis and its potential mechanisms in EC9706 and EC109 esophageal squamous carcinoma cells. EC9706 and EC109 cells were incubated with varying concentrations of aspirin and nimesulide, and the effects on cell proliferation and apoptosis were monitored by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide and flow cytometry. Reverse transcription-polymerase chain reaction and Western blot assays were used to investigate expression of Bcl-2 and Bax. Prostaglandin E2 production was measured by enzyme linked immunosorbent assay. Pretreatment with aspirin and nimesulide inhibited EC9706 and EC109 cell growth in a time and dose-dependent manner, accompanied with a decrease of prostaglandin E2 production. In EC9706 cells, the mechanism of aspirin and nimesulide induced growth inhibition was a consequence of cell cycle arrest at the G0/G1 check point. In EC109 cells, growth arrest was by induction of apoptosis, associated with downregulation of Bcl-2, but not Bax. In conclusion, aspirin and nimesulide could inhibit cell proliferation and induce apoptosis in esophageal squamous carcinoma cells. Cyclooxygenase-2 inhibitor may be a promising therapeutic agent for human esophageal squamous cell carcinoma.