Endoplasmic Reticulum (ER) is an organelle found in eukaryotic cells, responsible for intracellular calcium homocysteine, lipid synthesis, processing and folding of proteins. The cellular response that occurs in the event of increased folded or unfolded proteins is called endoplasmic reticulum stress. In order to adapt to changing environmental conditions, it is attempted to adapt with the Unfolded Protein Response (UPR), a mechanism that has been preserved evolutionarily. However, in cases where endoplasmic reticulum stress can not be resolved, cell death is triggered via apoptosis. Several molecules such as C/EBP-Homologous Protein (CHOP), A mitogen-activated protein kinase (MAP K) cascade, BCL2 associated X protein (Bax / Bak), Inositol-requiring enzyme 1 (IRE1) and caspase-12 are involved in endoplasmic reticulum stress induces apoptosis pathway. Endoplasmic reticulum stress has a great influence on cancer cell proliferation and survival. Recent investigations have shown that endoplasmic reticulum stress and unfolded protein response play an important role in cancer. Since the existence of some mechanisms that are not fully understood in the unfolded protein response triggered by endoplasmic reticulum stress has affected negatively the process of treatment, fully clarification of these mechanisms leads to understanding of diseases and the development of new treatment strategies. In this review, how the cancer cells can survive via endoplasmic reticulum stress response and proliferation will be discussed in the unfolded protein response axis and an overview will be given to the underlying molecular mechanisms.