It has been shown before that anisotropically microstructured surfaces exhibit anisotropic wetting phenomena. This study presents a possibility to control the anisotropy of wetting by tailoring the surface chemistry. PDMS microchannels were permanently hydrophilized and subsequently functionalized further. Thereby, systematic studies on the effect of the surface modification on the wetting properties of microstructures have been possible. Importantly, we found that the wetting parallel to the groove strongly depended on the chemical modification of the structure although the wetting perpendicular to the groove is almost unaffected. Through immobilization of a monolayer of Si nanoparticles (SiNPs) exclusively on the elevations of the hydrogel-coated microstructured PDMS substrate, the anisotropic wetting could be selectively altered unidirectionally along the pattern direction.