Cellobiose, a structural subunit of cellulose, was utilized as a retention promoter of polymer additives to a cellulose matrix in an aqueous papermaking system. beta-D-Cellobiosylamine was conjugated with anionic polyacrylamide (A-PAM) through a condensation reaction using water-soluble carbodiimide. Glyco-modified A-PAM containing cellobiose residues (CB-A-PAM), which was added to a pulp suspension using tap water, had good retention efficiency and enhanced the strength of paper sheets. Surface plasmon resonance analysis gave useful information on the affinity of CB-A-PAM for a cellulose matrix. Cellobiose and A-PAM had negligible interaction with cellulose, but CB-A-PAM was significantly adsorbed on the cellulose surface. It was presumed that the many cellobiose moieties in one CB-APAM molecule cooperatively enhanced its affinity for cellulose. Such sugar−sugar interaction is a novel concept for the retention system of papermaking additives and the functional design of carbohydrate-based materials.