Apolipoprotein E, a protein that is subject to structural changes at a water/lipid interface, is studied by molecular dynamics simulations performed in water and at a water/organic-phase interface. The protein backbone atoms get significantly more hydrated in the interfacial system than in the water simulation and undergo larger positional fluctuations. Larger fluctuations and hydration concur to be more manifest in the interfacial region of the aqueous phase. In this interfacial region, water is more structured and makes, relative to its number of neighbors, more hydrogen bonds than water in the bulk, a picture that has been previously inferred from molecular dynamics simulations of several water-organic liquid interfaces. We propose that the higher degree of protein hydration observed in the interfacial simulation arises from the structural behavior of interfacial water, which needs to make more H bonds and sees the protein as an additional partner. Our results are in agreement with spectroscopic data obtained for another apolipoprotein structurally similar to apolipoprotein E that show an increase in the protein hydration in the presence of a water/lipid interface and suggest that hydration is a factor helping the barrier crossing from the structure in aqueous solution to a partially folded conformation prone to bind to the lipids.