Stimuli-responsive supramolecular nano-systems (SRNS) have been a trending interdisciplinary research area due to flexibly being able to switch functions through exposure to appropriate stimuli, which makes the systems very attractive in multiple fields where precise control is key. Pillar[n]arenes, as a new generation of macrocyclic host molecules, possess captivating properties including versatile chemical modifiability, rigid electron-rich structure and tuneable size of the cavity, and have become extremely valuable molecules/building blocks in constructing SRNS via non-covalent interactions. Significantly, numerous SRNS based on pillar[n]arenes have been fabricated in the past few years and found extensive applications in hydrogels, sensors, bioimaging, diagnosis, and, importantly, controlled drug release. In this review, we highlight the advances of SRNS based on pillar[n]arenes, which are categorised in terms of response factors including pH, redox, enzymes, temperature, light and ions. The related applications of pillar[n]arenes are then summarized into the following areas: fluorescent chemosensors, drug delivery, molecular switches, and other functional materials. In addition, the future potential for construction of SRNS based on pillar[n]arenes and their applications are discussed.