In this study, for the first time a statistical analysis based on the response surface methodology (RSM) was employed to investigate individual and interaction effects of key operating parameters of the photocatalytic degradation under visible-light irradiation using Ag-S/PEG/TiO2. Ag-S/PEG/TiO2 is a visible-light-driven photocatalyst and was synthesized (based on earlier research) by co-doping of TiO2 with silver and sulphur and addition of polyethylene glycol (as a reagent template). In addition, the model pollutant was methylene orange (MO) and the studied operating parameters included the photocatalyst loading, initial concentration of the pollutant, and pH of the solution. The statistics-based experimental design and RSM was utilized to find a quadratic model as a functional relationship between the degradation efficiency and the three operating parameters. The regression analysis with R2 value of 0.9678 showed a close fit between the model prediction and experimental data of the degradation efficiency. The analysis of variance based on the model indicated that pH of the solution was the most influential factor, while the two other operating parameters were also significant. The efficiency of MO degradation reached 94.0% under the optimum conditions (i.e. photocatalyst loading of 1.20 g/L, MO concentration of 5 mg/L, and pH of 2).