This paper was to set up a novel effective technology to remove a persistent brominated flame retardant, which is called hexabromocyclododecanes (HBCDs). The core-shell Fe@Fe2O3 nanostructures were synthesized and adopted to activate persulfate to degrade HBCDs. Furthermore, the influences of pH value, the ratio of Fe@Fe2O3 and persulfate, and initial concentration of HBCDs on HBCDs reduction were studied. The results show that persulfate activated by core-shell Fe@Fe2O3 produced a large number of strong oxidation radicals. The degradation rate of HBCDs under acidic condition was higher than those under alkaline or neutral conditions. The Fe@Fe2O3 activator exhibited greater persulfate activation efficiency compared with the ferrous ions. The highest HBCDs removal rate (70%) was achieved at the ratio of Fe@Fe2O3: persulfate of 3:1. Therefore, core-shell Fe@Fe2O3 nanostructures are good activators of persulfate to degrade HBCDs.