Abstract: Metastasis is a multistep and low-efficiency biological process driven by acquisition of genetic and/or epigenetic alterations within tumor cells. These evolutionary alterations enable tumor cells to thrive in the inhospitable microenvironment they encounter in the process of metastasis and eventually lead to macroscopic metastases in distant organs. The unfolded protein response (UPR) induced by endoplasmic reticulum (ER) stress is one of the most important mechanisms regulating cellular adaptation to an adverse microenvironment. UPR is involved in all stages of metastasis, playing an important role in tumor cell growth, survival, and differentiation and the process of maintaining protein hemostasis. Sustained activation of ER stress sensors endows tumor cells with better epithelial–mesenchymal transition (EMT), survival, immune escape, angiogenesis, cellular adhesion, dormancy-to reactivation capacity in the process of metastasis. Here, we discussed the role of UPR in regulating the above-mentioned abilities of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.UPR in regulating the above-mentioned characteristics and mechanisms of tumor cells during metastasis, providing a reference for development of new targets for the treatment of tumor metastasis.