Abstract：Endoplasmic reticulum is a piping system interwoven in mammalian eukaryotic cells. A variety of physiological and pathological factors can lead to endoplasmic reticulum stress damage the cell. Because when the ERS the unfolded proteins and misfolded proteins increased in the ER, ER function disorder, which triggers the unfolded protein response. UPR can protect cells damage induced by endoplasmic reticulum stress, and recover the normal function of cells. This paper introduces the mechanism of the occurrence and development of UPR, and summarizes the latest research progress of UPR and hepatocellular carcinoma.