Chitosan oligosaccharide (COS) has been shown to regulate various cellular and biological functions. Epidermal growth factor (EGF) plays a significant role in tumorigenesis and invasiveness of some cancers. The aim of this study was to evaluate the effects of COS on EGF-induced cell growth and the further mechanisms. The results demonstrated that COS could inhibit EGF-induced epithelial GE11 cells proliferation in a dose dependent manner. In addition, EGF stimulated the epithelial cells to undergo morphological alteration, exhibiting mesenchymal cells higher metastatic and invasive potential, however, COS could partly suppress aforementioned morphological change. Signal transduction studies indicated COS repressed epidermal growth factor receptor (EGFR) phosphorylation and mitogen-activated protein kinase (MAPK) activation, but not Grb2, Ras, and Raf. Taken together, chitosan oligosaccharide inhibited EGF-induced cell growth and migration through blockade of the EGFR/MAPK signal transduction pathway. (C) 2017 Elsevier B.V. All rights reserved.