We have designed and characterized a DNA-based molecular switch which processes two physiologically relevant inputs: pH (i.e. alkalinisation) and enzymatic activity, and generates a chemical output (in situ synthesized oligonucleotide). The design, based on allosteric interactions between i-motif and hairpin stem within the DNA molecule, addresses such critical physiological system parameters as molecular simplicity, tunability, orthogonality of the two input sensing domains, and compatibility with intracellular operation/delivery.