Graft copolymerization of methacrylonitrile (MAN) onto chitosan using ammonium persulfate (APS) as an initiator was studied. The reactions were carried out under argon atmosphere in a homogenous aqueous phase containing a small portion of acetic acid (AcOH). Evidence of graft copolymerization was obtained by FTIR spectroscopy, e.g., the appearance of nitrile in the spectrum of chitosan- graft polymethacrylonitrile. The synthetic conditions were systematically optimized through studying the influential factors including temperature, as well as concentrations of initiator, MAN, AcOH, sodium dodecyl sulfate surfactant (SDS) and chitosan. The effects of individual factors were investigated by calculating and monitoring the variation of the grafting parameters, i.e., grafting ratio, grafting efficiency, add-on value, homopolymer content, and total conversion. The optimum condition was achieved at APS 0.0108 mol/L, MAN 0.201 mol/L, 80°C, SDS 0.0016 mol/L, chitosan 0.5 g, AcOH 0.0086 mol/L. The overall activation energy for the graft copolymerization was determined to be 7.3 kJ/mol.