The presence of natural organic matters (NOMs) will have a negative effect on the removal of small molecule organic contaminants in complex water quality, therefore, it’s very important to design a catalyst with size-exclusion function to achieve the selective removal of targeted pollutant. Herein, a novel ZIF-L catalyst precursor with lamellar stack structure is designed, and iron as heteroatom is doped in ZIF-L gaps named ZIF-L@Fe. After pyrolysis, Fe ions are transformed into Fe nanoparticles, and act as the active sites of catalyst. In order to verify the selective removal ability of resulted NSC@Fe in dielectric barrier discharge (DBD), tetracycline hydrochloride (TTCH) and humic acid (HA) is selected as the target pollutant and coexistence macromolecular interferent, respectively. In the presence of HA (50 mg/L), the degradation rate of TTCH in the system is not significantly affected (with HA, k = 0.037 min−1; without HA, k 0.036 min−1), which is mainly due to the layered material stacking characteristics (size-exclusion). The degradation mechanism and pathway are further confirmed by radical quenching experiments and liquid chromatography−mass spectrograph (LC−MS), respectively. This study is believed to shed new light on how to rationally design catalyst with selective removal of organic pollutants in complex water quality for water remediation.