We report a new route for the selective synthesis of di- and tetrafunctionalized pillararenes via oxidation and reduction of the pillararene units. Hypervalent-iodine oxidation of perethylated pillar[5]arene afforded pillar[5]arene derivatives containing one benzoquinone unit and two benzoquinones at the A,B- and A,C-units. A pillar[6]arene derivative containing one benzoquinone unit was also synthesized. Reduction of the benzoquinone units yielded position-selective di- and tetrahydroxylated pillararene derivatives. This methodology avoids the generation of many constitutional isomers and overcomes the isolation problem of numerous constitutional isomers. From these hydroxylated pillararenes, Huisgen reaction-based clickable di- and tetraalkynylated pillar[5]arenes were prepared. Because of the highly selective and reactive nature of Huisgen alkyne-azide cycloaddition, these pillar[5]arenes can serve as key compounds for a large library of di- and tetrafunctionalized pillararenes. Based on these di- and tetrafunctionalized pillar[5]arenes as key compounds, fluorescent sensors were created by the modification of di- and tetrapyrene moieties via Huisgen-type click reactions.