The variation of the single-chain mechanics of PNIPAM for the entire range of the methanol molar fraction (χ_methanol) (0 ~ 100%) in the water/methanol mixed solvent have been studied by AFM-based single-molecule force spectroscopy at RT. In general, the single-chain mechanics of PNIPAM shows a reentrant variation upon the change of χ_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 χ_methanol changes from 16% to 0.