Developing efficient catalyst materials for the degradation of antibiotic residues in wastewater is critical for the human health and ecological environment. In this study, CoOxclusters modified TiO2with oxygen vacancies (CoOx-TiO2(VO)) heterostructure was fabricated using a molten-salt method for efficient degradation of chloramphenicol (CP) through peroxymonosulfate (PMS) activation. By tuning the parameters in the synthesis procedure, the optimized CoOx-TiO2(VO) heterostructure achieved a 100% CP removal capacity within 240min in the presence of PMS. This is attributed to the existence of oxygen vacancies in TiO2, which provide a large number of free electrons that facilitate the electron migration from the CoOxcatalyst to PMS. Thus, the enhanced PMS activation facilitate the generation of •OH and SO4•-radicals, leading to the effective CP degradation. Furthermore, the applicability of CoOx-TiO2(VO)/PMS system was investigated under different operating parameters. This work highlights the potential for designing highly efficient heterogeneous catalysts for the treatment of wastewater containing antibiotic residues.