An efficient palladium-catalyzed copper-free Sonogashira reaction in water and acetone has been developed under mild conditions. The results showed that the aryl iodides could carry out the cross-coupling reaction with a variety of terminal alkynes in high yields in water-acetone in the absence of amine, copper(I) salts, or phosphine ligands at 60 °C for one hour, and good yields were obtained for aryl bromides at 60 °C for 12-24 hours in the presence of triphenylphosphine and piperidine. The method could be used to synthesize polyethynyl aromatic compounds in a one-pot reaction.