A novel method is presented here for trace determination of celecoxib by fluorescence detection using curcumin nanoparticles (CurNPs) loaded on multi-walled carbon nanotubes with carboxyl functional groups (CurNPs-MWCNT-COOH). For the synthesis of CurNPs-MWCNT-COOH, CurNPs were retained on carbon nanotubes with the aid of ultrasound waves. The sensing method is based on monitoring the quenching of synthesized CurNPs-MWCNT-COOH fluorescence by celecoxib. The morphology of CurNPs-MWCNT-COOH was studied by transmission electron microscopy (TEM) of the composite alone and in the presence of celecoxib. The effects of several parameters on the production of CurNPs-MWCNT-COOH and determination of celecoxib such as the Triton X-100 concentration, the amount of MWCNT-COOH and the pH were evaluated and optimum conditions were established. The calibration graph was found to be linear in the range of 20-220 ng mL-1 for celecoxib in the initial solution. The detection limit based on three times the standard deviation of the blank was 5.8 ng mL-1 for celecoxib and relative standard deviations (RSD) of 3.6% and 1.8% were obtained for eight replicate determinations of 60 ng mL-1 and 180 ng mL-1 of celecoxib, respectively. The method was applied to the determination of celecoxib in serum samples.