Decorin inhibits the transforming growth factor superfamily to stimulate skeletal muscle hypertrophy. The endoplasmic reticulum (ER) plays a crucial role in the synthesis and folding of proteins. The disruption of ER homeostasis affects protein folding and causes ER stress, which is associated with protein synthesis in muscle cells. The purpose of this study was to establish the mechanism by which decorin promotes myoblast proliferation and myotube hypertrophy as mediated by an ER stress-related pathway. Duck myoblasts were incubated for 24 h with tunicamycin. Our results show that tunicamycin triggered ER stress in myoblasts and led to an increase in protein synthesis via a decorin-dependent pathway. We then transfected the decorin gene into duck myoblasts in vitro, and the results demonstrated that overexpression of duck decorin increased myogenic determination factor and follistatin expression and decreased myogenin and myostatin expression. Moreover, the results demonstrated that overexpression of duck decorin led to higher expression of ER stress marker genes. This increased expression trend can be alleviated in vitro by 4-PBA, which is a chemical chaperone that inhibits palmitate-induced ER stress. Collectively, our data show that duck decorin promotes myoblast proliferation mediated by an ER stress-related pathway.