Liquid quantum dots (QDs) have been used as a fluorescent films sensor. Constructing a macroscopic, responsive, liquid QD system for lysine (Lys) is a challenging task. To achieve a selective macroscopic response towards Lys, herein we present a new strategy for integrating host-guest chemistry into a liquid QD system. Water-soluble pillar[ 5] arene WP5 was designed and synthesized as a host. WP5 was introduced onto the surface of PEG1810-modified QDs by host-guest interactions to obtain liquid WP5-1810-QDs. The interaction between WP5 and Lys is stronger than that between WP5 and PEG-1810, causing WP5 to be released from the 1810-QDs surface in the presence of Lys, resulting in macroscopic fluorescence quenching. This smart material shows promise in amino acid sensing and separation.