Perturbation of endoplasmic reticulum (ER) homeostasis leads to a stress condition described as "ER stress" which can induce the well-regulated program termed as unfolded protein response (UPR). The principal purpose of UPR is to reestablish the ER homeostasis. Some of the physiological and pathological situations that disrupt the homeostasis include hypoxia, glucose limitations, nutrient deprivation, low pH, genomic instability, and some cytotoxic compounds are frequently observed during the core formation and progression of tumors. These stressful microenvironments around the tumors affect the innate and adaptive immune responses. In addition, different immunoregulatory myeloid populations, like dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the tumor milieu and act as barriers to cancer immunotherapy. In these stressful situations, ER stress is usually induced to activate the UPR. Although the UPR mechanism is primarily a pro-survival process, preserved and/or prolonged excessive stress may induce cell apoptosis. Cancer and sustained ER stress may have modifications in ER stress mediated cell apoptosis and facilitate chronic inflammation and immune suppression within tumors. In this mini review, at first, we highlight the the role of UPR and its mediators in cancerous cells fate and then discuss their potential opportunities in cancer therapy. [ABSTRACT FROM AUTHOR]