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For fluoroquinolone antibiotics, which are widely present in groundwater in China and extremely hazardous, highly dispersed CoFe 2 O 4 nanoparticles (NPs) that can efficiently activate peroxymonosulfate (PMS) and rapidly degrade three fluoroquinolone antibiotics, were successfully prepared by the sol-gel method. The presence of Cl− and HCO 3 − reduced the degradation efficiency of CoFe 2 O 4 /PMS system for NOF, while H 2 PO 4 − showed a positive effect. The pH range for efficient degradation of fluoroquinolone antibiotics in the CoFe 2 O 4 /PMS oxidation system was between 3 and 9. Two reactive radicals, SO 4 −• and HO•, played an important role in the degradation process. The ability of the catalyst to degrade the antibiotics decreased from the initial 97.12%–88.72% after five repeated uses. The application of density-functional theory (DFT) indicated the chemical bonds in NOF that are vulnerable to free radicals (N13, C5, F19, and O20). Three degradation pathways of NOF were summarized in combination with the LC-MS results. The potential of the CoFe 2 O 4 NPs for practical applications in in situ remediation was verified by testing the migration ability and in situ degradation of NOF in two column experiments. Overall, this paper provides a theoretical basis for the practical application of nanomaterial-activated PMS in ISCO for groundwater remediation. [Display omitted] • The CoFe 2 O 4 /PMS system exhibited excellent degradation performance. • SO 4 −.• and HO• played an important role in the degradation process. • DFT combined with the LC-MS results summarized the degradation pathway of NOF. • The CoFe 2 O 4 NPs has potential applications in in-situ remediation. [ABSTRACT FROM AUTHOR]