A titanium dioxide/hydroxyapatite/ultraviolet (TiO2/HAP/UV-A) system was used to remove sulfamethoxazole (SMX) from water in a second-order response surface methodology (RSM) experiment with a three-level Box-Behnken design (BBD) for optimization. The effects of both the primary and secondary interaction effects of three photocatalytic reaction variables were examined: the concentration of SMX (X1), dose of TiO2/HAP composite (X2), and UV intensity (X3). The UV intensity and TiO2/HAP dose significantly influence the SMX and total organic carbon (TOC) removal (p<0.001). However, the SMX and TOC removal are enhanced with increasing TiO2/HAP dose up to certain levels, and further increases in the TiO2/HAP dose result in adverse effects due to hydroxyl radical scavenging at higher catalyst concentrations. Complete removal of SMX was achieved upon UV-A irradiation for 180 min. Under optimal conditions, 51.2% of the TOC was removed, indicating the formation of intermediate products during SMX degradation. The optimal ratio of SMX (mg L^(-1)) to TiO2/HAP (g L^(-1)) to UV (W/L) was 5.4145 mg L^(-1) to 1.4351 gL^(-1) to 18 W for both SMX and TOC removal. By comparison with actual applications, the experimental results were found to be in good agreement with the model's predictions, with mean results for SMX and TOC removal of 99.89% and 51.01%, respectively.