Hexanuclear zirconium metal-organic frameworks (Zr-6 MOFs) were successfully designed to possess different kinds of defects with various contents and its important influence on the capture of Se(VI) oxyanions was studied. The displaceable ligands (aqua and hydroxy groups) and weak-binding "capping" ligands (Cl-, O2C-CH3-, O2C-CF3- or O2C-CHF2-, HO- and/or H2O) on Zr-6 nodes could be substituted by Se(VI) oxyanions via a mechanism of anion-exchange. More efficient and faster uptake of Se(VI) oxyanions was obtained with the increase of the densities of both missing linker defects and missing cluster defects. Experimental findings as well as theoretical density functional theory (DFT) calculations disclosed that smaller HO-, Cl-, or H2O compensating ligands can be more easily substituted than the O2C-CH3-, O2C-CF3- or O2C-CHF2- compensating ligands. Based on DFT calculations, the binding energy of Se(VI) oxyanions toward defective UiO-66 is much higher than that of other heavy metals toward MOFs. Moreover, using modulator synthetic strategy in the preparation of Zr-6 MOFs can be a better choice for enhancing the removal capacity than synthesizing them with longer organic linkers which are too complex and expensive. The experimental results and theoretical calculations prefigure the great potentials of defect-tunable MOFs as promising candidates in the application of heavy metal ion remediation because they can be synthesized in large scale at low price and can also be elegantly tailored.