In this study, TiO2 nanospheres (TiO2-NS) were synthesized by the solvothermal method. Firstly, the synthesized nanomaterial was characterized by X-ray diffraction (XRD), Fourier Transformed Infrared (FTIR), scanning electron microscopy (SEM) and UV-Vis Diffuse Reflectance Spectroscopy (DRS). To study the photocatalytic degradation of Tartrazine (TTZ) and Naphthol Blue Black (NBB) in a binary mixture, the influence of some key parameters such as pH, pollutant concentration and catalyst dose was taken into account under visible and UV light. The results show a 100% degradation efficiency for TTZ after 150 min of UV irradiation and 57% under visible irradiation at 180 min. The kinetic study showed a good pseudo-first-order fit to the Langmuir–Hinshelwood model. Furthermore, in order to get closer to the real conditions of textile wastewater, the influence of the presence of salt on TiO2-NS’s photocatalytic performance was explored by employing NaCl as an inorganic ion. The optimum conditions provided by the Response Surface Methodology (RSM) were low concentrations of TTZ (2 ppm) and NBB (2.33 ppm) and negligible salt (NaCl) interference. The percentage of photodegradation was high at low pollutant and NaCl concentrations. However, this yield became very low as NaCl concentrations increased. The photocatalytic treatment leads to 31% and 53% of mineralization yield after 1 and 3 h of visible light irradiation. The synthesis of TiO2-NS provides new insights that will help to develop an efficient photocatalysts for the remediation of contaminated water.