Objective: To investigate the expression of endoplasmic reticulum oxidoreductin-1-like protein (ERO1L) in pancreatic cancer tissue and its clinical significance. Methods: The ERO1L mRNA expressions in 82 specimens of pancreatic cancer tissue and 12 specimens of normal pancreatic tissue adjacent to pancreatic cancer were determined by qRT-PCR method. The relations of ERO1L mRNA expression level with the clinicopathologic characteristics as well as the disease-free survival and overall survival rate of the pancreatic cancer patients were analyzed. Results: The relative expression level of ERO1L mRNA in pancreatic cancer tissue was significantly higher than that in adjacent normal pancreatic tissue (2.63 vs. 1.12, P<0.01). The expression of ERO1L mRNA was significantly associated with the degree of tumor differentiation, distant metastasis, clinical stage and lymph node metastasis of the patients (all P<0.05), but irrelevant to gender, age, tumor size and tumor location of the patients (all P>0.05). Survival analysis showed that the 1- and 3-year disease-free survival rate and overall survival rate in patients with high ERO1L mRNA expression was significantly lower than those in patients with low ERO1L mRNA expression (all P<0.01). The univariate and multivariate analyses revealed that ERO1L mRNA expression level was an independent risk factor for postoperative disease-free survival and overall survival in pancreatic cancer patients (both P<0.05). Conclusion: ERO1L expression is increased in pancreatic cancer tissue. The high expression of ERO1L is closely associated with the malignant clinicopathologic features of the pancreatic cancer patients and is also an independent prognostic factor for pancreatic cancer patients.