Polyacrylic acid (PAA), the synthetic homopolymer of acrylic acid, plays a key role in both pharmaceutical and cosmetic fields, for its rheological and mucoadhesive properties. These features may be enhanced and tuned by means of chemical or modifications, leading to new derivatives such as block copolymers, cross-linked gels, and amphiphilic polymers. The first two kinds of derivatives were already widely studied, while only few examples are described in literature of chemical derivatizations post-polymerization of PAA for the preparation of amphiphilic derivatives. In this study the preparation and the characterization of an innovative polymer for potential biomedical, cosmetic and pharmaceutical applications is reported. The new water-soluble polymer showed amphiphilic properties, due to the functionalization with cholesterol moieties. Furthermore, the new polymer is able to significantly improve the solubility of poorly water-soluble drug molecules.