The response surface method was applied to optimize operational factors in the solar photocatalytic process on the removal of Amoxicillin (AMOX) residues from aqueous solution using TiO2 immobilized on the sand as a catalyst. The results reveal that the degradation percentage of AMOX is 93.12%, when optimal conditions of pH=5, 75mg/l of TiO2, 400 mg/l of H2O2, and 10mg/l of AMOX concentration at 150 min irradiation time were used. Furthermore, the model's expected response results have reasonable similarity with the actual data (R2 =93.58%), demonstrating the efficiency of this method in making an accurate prediction. A second-order polynomial multiple regression model was used to evaluate the responses, which confirms that was a satisfactory adjustment with the achieved data through analysis of variance (R2=93.58%, R2adj =91.48% and R2pred=89.68%). In addition, it is observed that the removal of undesirable compounds follows a pseudo-2nd order kinetic model with R2 =0.9862. In conclusion, with the ease of usage of immobilized TiO2 and good photocatalytic efficiency, the findings showed the potential application to the antibiotics from an aqueous solution.