AbstractIntegrating dynamic DNA nanotechnology with protein‐controlled actuation will expand our ability to process molecular information. We have developed a strategy to actuate strand displacement reactions using DNA‐binding proteins by engineering synthetic DNA translators that convert specific protein‐binding events into trigger inputs through a programmed conformational change. We have constructed synthetic DNA networks responsive to two different DNA‐binding proteins, TATA‐binding protein and Myc‐Max, and demonstrated multi‐input activation of strand displacement reactions. We achieved protein‐controlled regulation of a synthetic RNA and of an enzyme through artificial DNA‐based communication, showing the potential of our molecular system in performing further programmable tasks.