Estrogen receptor (ER)‑α36, a novel isoform of ER, primarily mediates non‑classical estrogen signaling. It has been reported that ER‑α36‑mediated growth stimulating signals are involved in the malignancy of gastric tumor cells. However, the mechanism underlying the regulation of ER‑α36 function in development of gastric cancer remains to be elucidated. The present study investigated the role of 78 kDa glucose‑regulated protein (GRP78) in the regulation of ER‑α36 expression and signaling during the growth of gastric tumor cells. It was demonstrated that GRP78 expression was detectable in gastric cancer tumor tissues, and was positively‑correlated with tumor stage, lymphatic metastasis and ER‑α36 expression (P<0.05). An increased growth rate, and increased expression of ER‑α36 and the cell cycle regulator cyclin D1 was detected in cells with GRP78 overexpression (SGC‑High78 cells). SGC‑High78 cells are more sensitive to estrogen compared with SGC‑Control cells. Therefore, the results of the present study demonstrated that GRP78 positively regulated ER‑α36 expression and signaling with cell growth in gastric cancer, which is involved in gastric carcinogenesis.