Constructing binding pockets by hierarchically assembling tailored building blocks and understanding structure-property relationships are challenging goals. Herein, amphiphilic pillar[5]arene and pillar[6]arene were prepared and used to construct 2D sheets, which consisted of well-defined hydrophobic and hydrophilic interlayers. In the hydrophobic interlayers, internal hydrophobic pockets were created by packing pairs of pillar[