Photocatalytic degradation is an eco-friendly and sustainable method for the treatment of water pollutants especially tetracycline hydrochloride (TCH). Herein, we developed F-doped H₂Ti₃O₇-{104} nanorods with oxygen vacancies using TiOF₂ as a precursor by simple alkali hydrothermal and ion-exchange methods. The phase structure, surface composition, optical properties, specific surface areas and charge separation were analysed by a series of measurements. The effects of KOH concentration on the structure and properties of H₂Ti₃O₇ were investigated. It is confirmed that the TiOF₂/H₂Ti₃O₇ composite can be formed in low concentration KOH solution (1 mol L⁻¹), while the H₂Ti₃O₇ single phase can be formed in high concentration KOH solution (>3 mol L⁻¹). The prepared F-doped H₂Ti₃O₇-{104} nanorods provide a high specific surface area of 457 m² g⁻¹ and a macroporous volume of 0.69 cm³ g⁻¹. The appropriate mesoporous structure of the photocatalyst makes TCH have a stronger affinity on its surface, which is more conducive to the subsequent photodegradation. Moreover, a synergistic mechanism of photosensitization and ligand–metal charge transfer (LMCT) in the photocatalytic degradation of TCH was proposed. In addition, the prepared F-doped H₂Ti₃O₇-{104} nanorods showed excellent cycle stability and resistance to light corrosion. After five cycles of photodegradation, the degradation rate of TCH was only reduced from 92% to 83%. This low-cost strategy could be used for the mass production of efficient photocatalysts, which can be used for TCH clean-up in wastewater treatment.