In this study, the photocatalytic degradation of Norfloxacin (NOR) has been studied using N-doped TiO2 (N–TiO2) under visible light irradiation, which was synthesized from a self-owned patent recipe and procedure. Subsequently, a three-factor five-level model, which was based on the central composite design (CCD), was developed to determine the optimal NOR concentration, N–TiO2 dosage, and initial pH in practical use. Meanwhile, the degradation pathway was identified by high-performance liquid chromatography-mass spectroscopy (HPLC-MS). Moreover, the toxicity of degradation intermediates was determined using the bacterium Escherichia coli so as to evaluate the health risk of the photocatalytic treated influent. The synthesized N–TiO2 nanoparticles were spherical, and the grain sizes were distributed from approximately 12 nm–20 nm, with a specific surface area of 148.52 m2/g. The light absorption is range from the ultraviolet region to the visible light region since the band gap was reduced to 2.92eV. It was demonstrated from the response surface method results that the initial NOR of 6.03 mg/L, N–TiO2 dose of 0.54 g/L, and pH of 6.37 could be the proposed optimal degradation conditions, which resulted in a 99.53% removal of NOR within 30 min under visible light irradiation. Two possible degradation pathways were proposed, including the replacement of F atoms by hydroxyl radicals, piperazinyl ring cleavage, hydroxylation, and decarboxylation. In the acute toxicity test, the toxicity declined 55% after photocatalytic treatment for 60 min. The results show the feasibility and novelty for photocatalytic treatment of antibiotics by N–TiO2 photocatalyst.