GRP78 is a classical endoplasmic reticulum (ER)-localized protein, acting as a chaperone and master regulator of the unfolding protein response in this location. Interestingly, under certain conditions, GRP78 is also located at the cell surface. More concretely, it was observed at the cell surface of several types of cancer cells, but also of trophoblastic cells and stressed cells in general. Cell surface GRP78 can bind to extracellular proteins and promote the activation of different signaling pathways. One of these proteins is prostate apoptosis response 4 (Par-4), a pro-apoptotic protein which is secreted by cancer cells. It was observed that the secretion of Par-4 was increased in parallel with GRP78 cell-surface localization, suggesting a relationship between these events. In this review, we discuss the role of Par-4 in GRP78 relocation at the cell surface.