ObjectiveTo summarize the progress of study on the relationship between endoplasmic reticulum stress and cell proliferation and provide evidence with reliable evidence-based data to the experiment on the field of tissue damage repair, organ proliferation, and regeneration.MethodThe relevant literatures about the progress of multiple signaling pathways related to the endoplasmic reticulum stress in the cell proliferation and injury repair in recent years were reviewed.ResultsThe endoplasmic reticulum stress participated in the process of proliferation and regeneration in the intestinal epithelial cells, skeletal muscle cells, islet cells, and hepatocytes through different pathways, which involved the three pathways of unfolded protein reaction that interacted with interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, Wnt, etc.ConclusionsAlthough endoplasmic reticulum stress has been widely debated in the field of determining cell fate, after we reviewed recent studies on endoplasmic reticulum stress in maintaining cell survival and promoting cell proliferation, the complexity, diversity, and importance of the endoplasmic reticulum stress in promoting cell proliferation have been presented in front of us. It not only promotes cell proliferation through the classical signaling pathway with Wnt protein, but also acts to repair tissue and promote proliferation by interacting with Musashi protein independently of the Notch pathway. The complex reaction pathway interacts with different stimulating factors in different cells, providing research directions and exploration possibilities for cell proliferation, injury repair, and organ regeneration, reveales the critical role of endoplasmic reticulum stress in cell proliferation.