In this study, TiO2/CeO2 hybrid photocatalysts were prepared from a powder mixture of the corresponding component solid oxides. X-ray diffraction (XRD), UV-vis diffuse reflectance spectroscopy (DRS), transmission electron microscopy (TEM), and N-2 physisorption techniques were used for the characterization of prepared photocatalysts. The synthesis variables were optimized in the photocatalytic removal of phenazopyridine (PhP) as a model drug contaminant using response surface methodology (RSM). The results showed that the predicted data from RSM was found to be in good agreement with the experimental results with a correlation coefficient (R-2) of 0.9518. Optimization results showed that maximum removal efficiency was achieved at the optimum synthesis conditions: Ti/Ce weight ratio of 0.84:0.16, calcination temperature of 502 degrees C, and calcination time of 62 min. Results also showed that coupling TiO2 with CeO2 could produce special electrons and holes transfer from TiO2 to CeO2 which is able to facilitate the separation of the electron-hole pairs and thus improve photocatalytic activity of the hybrid photocatalyst. Effect of synthesis variables on the removal efficiency of PhP was estimated by the response surface and contour plots. The obtained results clearly demonstrated that experimental design approach was one of the reliable methods for modeling and optimization of the synthesis variables.