An efficient and reusable pH-responsive mesoporous silica nanocomposite shuttle-supported palladium catalyst was synthesized, which efficiently promotes the Sonogashira reaction in water-based biphasic systems. This catalyst of shell-embedded palladium nanoparticles is highly dispersed in organic phase in a pH range from 9 to 10 just like a homogeneous catalyst, and can be separated and reused like a heterogeneous one by adjusting the pH value of the aqueous medium. In addition, Sonogashira reactions can be performed without a copper co-catalyst. Copyright (C) 2015 John Wiley & Sons, Ltd.