The variation of the single-chain mechanics of poly(N-isopropyl-acrylamide) (PNIPAM) for the entire range of the methanol molar fraction (chi(methanol)) (0%-100%) in the water/methanol mixed solvent has been studied by AFM-based single-molecule force spectroscopy at room temperature (RT). In general, the single-chain mechanics of PNIPAM shows a reentrant variation upon the change of chi(methanol) from 0% to 100%. The possible mechanism for the reentrant variation of the single-chain mechanics is discussed. The current study may cast new light on the design of novel environmental responsive nano-devices in the future, when chi(methanol) changes from 16% to 0%. (C) 2013 Elsevier Ltd. All rights reserved.