Control over the orientation of cylindrical and lamellar domains is required for pattern transfer in block copolymer lithography. Previous work mainly focuses on the use of random copolymer brushes to control the wetting behaviors of block copolymers (BCPs), but random copolymerization is only limited, to a few monomer pairs. Here we demonstrate the use of homopolymer brushes/mats to modify the substrate to form a chemically homogeneous surface. The surface affinity is tuned by changing the monomer substituent, and a variety of wetting behaviors are obtained in BCP films on homopolymer brushes/mats. Three series of hydroxy-terminated or cross-linkable homopolymers, including polymethacrylate, polyacrylate, and polystyrene derivatives, are prepared for controlling the BCP substrate interaction. Both preferential and nonpreferential wetting behaviors of poly(styrene-b-methyl methacrylate), poly(styrene-b-rac-lactide), and poly (styrene-b-propylene carbonate) films are obtained as the homopolymer structures change in terms of the carbon contents, indicating that this homopolymer approach may be applicable to any BCPs. Moreover, homopolymer brushes can also substitute random copolymer brushes in directed self-assembly of BCP films with density multiplication on the chemical pattern. The use of homopolymer brushes/mats may have advantages over random copolymer brushes or blend brushes in terms of reproducibility and uniformity of brush formation, reduction of defect density, and increase of assembly kinetics.