Iron-based catalysts are widely used in water treatment and environmental remediation due to their abundant content in nature and their ability to activate persulfate at room temperature. Here, eggshell biochar-loaded natural iron slag (IO@ESBC) was successfully synthesized to remove tetracycline hydrochloride (TCH) by activated persulfate. The morphology, structure and chemical composition of IO@ESBC were systematically characterized. The IO@ESBC/PS process showed good performance for TCH removal. The decomposition rate constant (k) for IO@ESBC was 0.011 min−1 and the degradation rate was 3690 mmol/g/h in this system. With the increase of PS concentration and IO@ESBC content, the removal rate of TCH both increased. The IO@ESBC/PS process can effectively remove TCH at pH 3–9. There are different effects on TCH removal for the reason that the addition of water matrix species (humic acid, Cl−, HCO3−, NO3− and HPO42−). The IO@ESBC/PS system for degrading TCH was mainly controlled by both the free radical pathway (SO4•−, •OH and O2•−) and non-free radical pathway (1O2). The loading of ESBC slows down the agglomeration between iron particles, and more active sites are exposed. The removal rate of TCH was still above 75% after five cycles of IO@ESBC. This interesting investigation has provided a green route for synthesis of composite driving from waste resources, expanding its further application for environmental remediations.