Sericin is a type of high molecular weight water-soluble glycoprotein surrounding fibroin (silk protein) that has been used as a cell culture supplement and accelerates cell proliferation in various serum-free media. The purpose of this study was to investigate the enhancing effect of thyroglobulin (Tg) secretion by sericin in thyrocytes, FRTL-5 cells. While Tg-mRNA expression was not enhanced, a secreted form of Tg was obviously increased by sericin. In this status, expression of both endoplasmic reticulum (ER) molecular chaperones (Bip & calreticulin) and ER membrane proteins (IRE1, PERK & ATF6) was enhanced. The proximal step of IRE1, XBP1 mRNA splicing was slightly detected however, the proximal step of PERK, phosphorylation of eIF2α, was changeless. In addition, sericin enhanced cell viability by the MTT assay. The above results showing the ability of sericin to promote protein production demonstrated its potential usefulness as a new biomaterial.