The remarkable efficiency of biological chemical reactions is the result of evolution and many of these reactions are promoted by confined water. This has inspired significant research endeavors exploiting the potential of this special water in chemistry. However, these systems are so far limited to complex artificial solids or biphasic systems and small molecules as reactants. Here, we show that the intrinsically present surface-confined water in hierarchically structured biopolymers can be used as nanomedium to promote chemical reactions. We found in the example of cellulose fibers that confined water was actively involved in the reaction mechanism and facilitated the surface acetylation of the fiber, increasing reaction kinetics, efficiency and regioselectivity. Our findings can be regarded as proof-of-principle that the hydration layer in nanoporous polymers can be exploited as medium to promote chemical reactions at their surface. This concept can likely be extended to other polymers and various reaction systems.