Chemically manipulating phenylalanine’s purely hydrocarbon side chain in living systems is challenging. Now this has been achieved through biocompatible, palladium-triggered decaging of iodine-caged phenylalanine. This enables on-demand control of live-cell hydrophobic interactions as well as π interactions, which spans from fluorophore activation and peptide disassembly to protein binding and tumour–immune cell recognition.