Glucose deprivation is a factor evoking endoplasmic reticulum (ER) stress and induction of expression of an oxygen-regulated protein of 150 kDa (ORP150). We studied the effect of inducible overexpression of ORP150 on senescence and apoptosis of human breast carcinoma cells (MCF7) and human skin fibroblasts. We found an inhibitory effect of ORP150 on apoptosis and senescence of MCF7 cells, but not fibroblasts in ER stress conditions. An increased expression of senescence-associated β-galactosidase and acid β-galactosidase activity (biomarkers of cellular senescence) was observed. We suggest that ORP150 induction in cancer cells can promote tumour progression and may be a major cause of their resistance to chemotherapeutics.