In this work we report preparation TiO2 hollow spheres and its application as an electrochemical sensor. Therefore the novel carbon paste electrode modified with TiO2 hollow spheres (TOHS), multi-walled carbon nanotubes (MWCNTs) and poly-glutamic acid (PGA) film (PGA/TOHS/MWCNTs/CPE) was used for simultaneous determination of dopamine (DA) and piroxicam (PRX) in the presence of ascorbic acid (AA). The electro-oxidation of dopamine(DA) and piroxicam (PRX) has been investigated by application of the modified electrode using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry (CA) methods. The modified electrode accelerates the electron transfer reactions of DA and PRX. In addition it shows no significant interference of AA as the electroactive coexistent compounds with DA and PRX in biological systems. The fabricated sensor revealed some advantages such as excellent selectivity, good stability and high sensitivity toward DA and PRX determination. Under the optimum conditions the electrode provides a linear response versus DA and PRX concentrations in the range of 0.3–60 and 0.4–80 µM and with a detection limit of 0.2µM and 0.3µM(S/N=3) respectively using the DPV method. The modified electrode was used for determination of DA and PRX in human urine with satisfactory results.