Our previous study demonstrated that COX-2 selective inhibitor celecoxib antagonized the cytotoxic action of cisplatin and carboplatin through COX-2-independent mechanisms.Whether celecoxib also affects the anticancer activity of oxaliplatin is largely unknown.The aim of this study was to determine the impact of celecoxib on oxaliplatin efficacy in human esophageal cancer cells.Celecoxib antagonized the cytotoxicity of oxaliplatin whereas knockdown of COX-2 by specific siRNA failed to phenocopy the antagonizing effect ofcelecoxib, indicating its action is not reliant on COX-2 inhibition.Further study revealed that the antagonizing effect of celecoxib was associated with decreased intracellular oxaliplatin accumulation.Reduced influx, accompanied by the reduction of protein level of organic cation transporter 1 and 2, accounts for decreased intracellular drug accumulation.In addition, combined treatment did not show benefit compared with oxaliplatin or celecoxib monotherapy in vivo.Therefore, clinical trials with celecoxib in combination with oxaliplatin should be approached with caution.