In the present study, we demonstrated that i) human pancreatic cancer cell lines expressed GRP78; ii) ER stress induced by thapsigargin upregulated protein levels of GRP78 in human pancreatic cancer cell lines; iii) ER stress-related molecules downstream of GRP78 were expressed at various levels according to the respective human pancreatic cancer cell lines; and iv) finally, knockdown of GRP78 by siRNA enhanced PARP cleavage in the human pancreatic cancer cell lines. The gene discussed is HSPA5; the disease is familial pancreatic carcinoma.