In this research paper, Box-Behnken design (BBD) combined with response surface methodology (RSM) has been applied to optimize phenol photocatalytic degradation. In this process, nano-structured copper-doped titanium dioxide was used as the photocatalyst. The experiments were conducted in the presence of H2O2 and under the UV irradiation. The operational factors were initial phenol concentration, reaction time, and Cu/TiO2 dosage. The effects of process variables as well as their binary interactions were modeled. High values of determined R2-coefficients of the model (>0.99) confirm that the proposed equation fits the experimental data accurately. The fundamental objective of this work was to determine the most important parameter of the mentioned process. The ANOVA results enunciated that the significance of the parameters is follows (the most to least significant): Cu/TiO2>time>initial phenol concentration.