All eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by signaling an adaptive pathway termed the unfolded protein response (UPR). Glucose-regulated protein (Grp) 78 is a molecular chaperone involved in the UPR. The aim of this study was to detect Grp78 expression in lung cancer using immunohistochemical (IHC) staining, and also to evaluate the relationship between the Grp78 expression level and the prognosis of patients with lung cancer. We used immunohistochemistry to analyze the protein expression of Grp78 in paraffin-embedded tumor samples from 132 well-characterized lung cancer patients and compared the expression level of Grp78, clinical variables and survival outcome. A positive expression of Grp78 was detected in the cytoplasm of tumor cells in 88 of the 132 patients (66.7%) with lung cancer. No significant difference was observed between the Grp78 expression and the gender, age at operation, histological type, pathologic stage, pathologic T status, and pathologic N status. Lung cancer patients with a positive Grp78 expression tended to show a better prognosis than those with a negative Grp78 expression. In addition, a multivariate analysis of the clinicopathologic characteristics of lung cancer indicated a positive expression of Grp78 to be a significant factor for predicting a favorable prognosis (p < 0.001, risk ratio = 2.35). A positive expression of Grp78 may thus be a useful marker for predicting a favorable prognosis in patients undergoing a resection of lung cancer. The ER stress pathway mediated by Grp78 may therefore be responsible for controlling the growth of lung cancer cells.