Metal-organic frameworks (MOFs) have great potential for the capture of volatile iodine. The effect of a precise regulation of active sites in JLNU-4 (MOFs) on capture of iodine was investigated by Monte Carlo (MC) method and molecular dynamics (MD), and it was found that the larger the Zn/Cd atomic ratio, the better the iodine capture. Interestingly, compared with the meta-position regulation of Zn/Cd, the ortho-positions regulation increased the free volume of the crystal and enhanced the interaction between Cd and I, thus improving the capture capacity of iodine. The first-principles study revealed the charge transfer of each atom in the MOFs crystal with I2 during iodine capture and the secondary bonds with weak covalent interactions were all formed after I2 adsorption onto MOFs. These findings provide a reference for the capture of radioactive iodine and a theoretical basis for the strategies for precise regulation of MOFs in the future.