Oxidized starch-graft-poly(styrene-butyl acrylate)[OS-g-P(ST-BA)] latex with core-shell structure was synthesized by the graft copolymerization of OS with ST and n-butyl acrylate (BA) via emulsion polymerization. A three-level, four-variable Box-Behnken design was employed to investigate the effects of the concentration of OS, initiator, monomers, and temperature on the graft copolymerization. The significance of variables and their interactions were analyzed using analysis of variance and the model's significance was confirmed. The OS-g-P(ST-BA) was characterized by FTIR, TEM, DSC, and dynamic light scattering. The core-shell structure of OS-g-P(ST-BA) particle was clearly shown in TEM micrographs and confirmed by DSC analysis. Application of the OS-g-P(ST-BA) latex as a binder in paper coating improved the gloss, print gloss, and picking resistance of coated paper.