Stimuli-responsive hyperbranched polymers have attracted great attention in recent years because of their wide applications in biomedicine. Through proton-transfer polymerization of triethanolamine and 1,2,7,8-diepoxyoctane with the help of potassium hydride, a series of novel backbone therm and pH dual-responsive hyperbranched poly(amine-ether)s were prepared successfully in one-pot. The degrees of branching of the resulting polymers were at 0.40-0.49. Turbidity measurements revealed that hyperbranched poly(amine-ether)s exhibited therm and pH dual-responsive properties in water. importantly, these responsivities could be readily adjusted by changing the polymer composition as well as the polymer con-centration in aqueous solution. Moreover, in vitro evaluation demonstrated that hyperbranched poly(amine-ether)s showed low cytotoxicity and efficient cell internalization against NIH 3T3 cell lines. These results suggest that these backbone therm and pH dual-responsive hyperbranched poly(amineether)s are promising materials for biomedicine. (C) 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 49: 966-975, 2011