The rational design and preparation of monolayer metal-organic framework (MOF) nanosheets remain great challenges. Recently, we found that monolayer MOF nanosheets can be facially exfoliated on a large scale from pristine two-dimensional (2D) MOFs with substantially reduced interlaminar interaction. By employing cage-like bicyclocalix[2]arene[2]triazine tri-imidazole as the building block, a family of cationic two-dimensional metal-organic frameworks (2D MOFs) with steric layer were designed and prepared. The single crystal structures have clearly identified that only very weak and sparse distributed C-H···π interaction exists between adjacent layers.On the basis of density functional theory calculation, the interlayer interaction of these cage-based cationic 2D MOFs was estimated to be 1/46th of that of graphite. Due to the extremely weak interaction, these cationic 2D MOFs tend to degenerate into an "amorphous" state after being soaked in other solvents; they can be readily exfoliated into 1.1 nm thick monolayer nanosheets with a high degree of thickness homogeneity, large lateral size, and significantly enlarged surface area. This work has identified that a cage-like molecule is the ideal building block for 2D cationic MOFs and ultrathin nanosheets; It was futher confirmed that weakening the interlaminar interaction is an effective strategy for facilely producing monolayer nanosheets.