The aim of this work is to investigate the stabilization of the conformation of adsorbed human serum albumin (HSA) on surfaces containing CF3 and/or OH groups. These groups are structural characteristics (mimics) of trifluoroethanol, which is known to stabilize the secondary structure of several proteins. We focused on three different types of organic surfaces: (i) self-assembled monolayers (SAMs) prepared from mixtures of thiols with CF3 and OH end groups, (ii) polymer surfaces of a poly(vinyl methyl ketone) (PVMKCF3/OH), which was modified with OH and CF3 groups, and (iii) surfaces of polymer fluorosurfactant complexes containing CF3 groups. It was revealed that the secondary structure of HSA in contact with the SAMs depends on the thiol composition. SAMs of mixed monolayers displayed the highest HSA recognition measured by antibody binding. CD measurements showed that PVMKCF3/OH surfaces retain the secondary structures of adsorbed HSA. Examples of polymer fluorosurfactant complexes are given that retain the secondary structure of adsorbed HSA and a complex that increase the content of alpha-helices. A combination of CF3 and OH groups is proposed as a new approach to prepare biocompatible surfaces.