In this paper, TiO2-based geopolymer microspheres (TiO2@GMs) were prepared by dispersion-suspension-solidification technique using water glass activated metakaolin-based geopolymer slurry as a binder. The effects of different factors on the sphericity and particle size of TiO2@GMs were investigated, and the order of importance was found to be TiO2 dosage > water volume > water glass modulus > rotation speed. Secondly, in the Fenton system under UV light irradiation, TiO2@GMs exhibited excellent performance in the degradation of tetracycline hydrochloride (TC). At a TC concentration of 20 mg/L, liquid-to-solid ratio of 0.3 g/L, H2O2 (30 wt%) of 10 mM, and pH = 4.47, 98.6% TC was degraded by TiO2@GMs within 30 min TiO2@GMs can be easily separated from the reaction product and showed excellent recycling performance, with a degradation efficiency of 90.6% after five success reuses. Finally, a plausible photocatalytic degradation mechanism of TiO2@GMs for TC was discussed. This newly designed TiO2@GMs composite can be deemed as an alternative material for the degradation of TC and other similar antibiotic on large scale.