Silica supports could constitute interesting stationary phases for the separation of biological substrates by affinity chromatography because of their better mechanical strength compared to polymers. Pore sizes and surface areas of the supports should be large enough (>70 nm) to provide high binding capacity and high mass transfer. However, most commercially available large-pore silicas usually exhibit very low surface areas. In the present work, we show how to increase the surface area of macroporous (80 nm) low surface area (16 m 2 /g) silica particles by a pseudomorphic transformation process occurring only at the surface of the pores, while preserving the macropores and the particle sizes of the parent silica. The transformation occurs through a controlled dissolution/reprecipitation mechanism in the presence of longchain alkylammonium surfactants. Consequently, the surface area of these macroporous silica materials was increased by a factor of 10 to 20 and was tuned between 100 and 300 m 2 /g. Moreover, this higher surface area allows the amount of functional groups immobilized at the surface of the materials to be increased by covalent grafting. The anchorage of glycidoxy groups at the surface of these new silicas produce materials with a high binding capacity for further protein coupling, comparable to polymeric phases. These new silica phases feature a high mechanical stability and represent an attractive alternative to polymeric phases in the area of large molecule separations.