The catalytic performances of magnetic NixFe3-xO4 catalysts in persulfate (PS) activation for tetracycline (TC) degradation are first investigated. In this study, NixFe3-xO4 catalysts with variable compositions (x = 0.2, 0.6 and 1.0) were synthesized. The physical and chemical characteristics of NixFe3-xO4 catalysts were investigated systematically. NixFe3-xO4 catalysts have sheet-like morphology and spinel type structure. In NixFe3-xO4/PS system, sulfate radical (SO4 center dot-) and hydroxyl radicals (HO center dot) produced by PS activation degraded TC efficiently. In the comparation of different NixFe3-xO4 catalysts, Ni0.6Fe2.4O4 presented superior catalytic activity performance. The optimum degradation rate in 86% was obtained at Ni0.6Fe2.4O4 = 350 mg/L, PS = 42.0 mu M and pH = 7 after 35 min reaction. The main radicals (SO4 center dot- and HO center dot) were identified by scavengers and the electron spin resonance (ESR) experiment. Meanwhile, possible activation and degradation mechanism were analyzed thoroughly. The high catalytic efficiency and short degradation period of Ni0.6Fe2.4O4 catalyst indicate that it has great potential in TC wastewater disposal and environmental protection.