Free radicals are closely related to the occurrence and development of aging, cancer and inflammation. The aim of the present study was to improve the antioxidant effects of quaternary ammonium chitosan (QCS) by modified with silk fibroin peptide (SFP). The modification had been confirmed by FT-IR and 1H NMR spectroscopy. Degree of substitution (DS) of QCS-SFP could be controlled by adjusting the reaction conditions. In this paper, the results of moisture absorption and retention test showed that QCS-SFP had excellent moisture absorption and retention properties. In vitro antioxidant activity assays demonstrated that, with the DS and concentration increasing of QCS-SFP, the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydroxyl radical and hydrogen peroxide (H2O2) increased. Furthermore, the methyl thiazolyl tetrazolium assay (MTT) was applied to evaluate the biocompatibility of QCS-SFP, and the result indicated that QCS-SFP with the DS of 0.32 displayed pronounced cell viability at 100ppm. These results suggested that QCS-SFP would appear to be a promising candidate for wound dressing application.