Objective: To investigate the effect and related mechanism of nonsteroidal anti-inflammatory drugs, such as celecoxib and indomethacin, on the proliferation and apoptosis of gastric cancer cells MKN45. Methods: The effect of celecoxib and indomethacin of various concentrations on the proliferation of MKN45 in gastric cancer cells was measured by MTT assay. After cells were treated with nonsteroidal anti-inflammatory drugs alone or accompanied with P38MAPK pathway inhibitor SB203580, cell cycle distribution and cell apoptosis were detected by flow cytometry, respectively. Furthermore, the protein expression of COX2, p-P38MAPK and P38MAPK was measured by Western blot. Results: MTT assay showed that both celecoxib and indomethacin inhibited the proliferation of MKN45 in gastric cancer cells in vitro with a concentration dependent manner. flow cytometry showed that nonsteroidal anti-inflammatory drugs restrained the cell cycle G1/S transition and accompanied use of SB203580 could partly reverse the inhibitory effect of nonsteroidal anti-inflammatory drugs. Detection of cell apoptosis showed that nonsteroidal anti-inflammatory drugs up-regulated the protein expression of P53 and cleaved-caspase3/caspase3, promoted MKN45 cell apoptosis; while accompanied use of SB203580 down-regulated the protein expression of P53 and cleaved-caspase3/caspase3 and decreased cell apoptotic rate in celecoxib group or indomethacin group. Furthermore, cells treated with nonsteroidal anti-inflammatory drugs exhibited higher COX2 protein expression and lower p-P38MAPK/P38MAPK protein expression; while accompanied used of SB203580 partly reverse its effect. Conclusion: Nonsteroidal anti-inflammatory drugs could inhibit the proliferation of MKN45 in gastric cancer cells and promoted its apoptosis via P38MAPK pathway.