The great harm of antibiotic residues in medical wastewater to the ecological environment and human health has become the focus of social attention. Herein, we designed a new peroxymonosulfate (PMS) activation system by in-situ anchoring NiFe-LDH nanosheets into CeO2 (NFC) as a heterogeneous photocatalyst to degrade pollutants. The NFC/PMS/Vis system showed excellent and rapid degradation effect on tetracycline (TC) under the synergistic effect of photocatalysis and PMS activation, and the removal rate of TC was about 98.8 % within 40 min. The chemical compositions, microstructures, and optical properties of synthesized photocatalysts were studied by a series of characterization methods such as XRD, XPS, SEM, TEM and UV-DRS. The effects of various reaction systems and operating parameters such as initial concentration, catalyst dosage, and PMS concentration on the degradation efficiency of TC over optimized NFC-4 composite were investigated. The active species in the reaction system and the dominant SO4− were confirmed by quenching tests and electron paramagnetic resonance (EPR) measurements, and a plausible photocatalytic mechanism for PMS activation and pollutant remediation was further proposed.