S100A11 is a member of S100 protein family, and our previous study showed that S100A11 is one of the up-regulated proteins that have not been reported to be associated with pancreatic carcinoma. The purpose of this study was to investigate the relation between S100A11 expression and the clinicopathological variables and clinical outcome in patients with pancreatic adenocarcinoma. Immunohistochemistry analysis was performed for S100A11 in 78 pairs of specimens of human pancreatic adenocarcinoma tissues and adjacent nontumorous tissues. The univariate and multivariate survival analyses were also performed to determine its prognostic significance. S100A11 expression in pancreatic adenocarcinoma (62/78) was significantly higher than that in the adjacent nontumorous tissues (19/78) (P = 0.000). High expression of S100A11 was associated with the lymph node metastasis and histological differentiation (P = 0.003 and 0.004, respectively). Univariate analysis showed that S100A11 expression was associated with poor prognosis (P = 0.0000). Multivariate analysis using the Cox regression model indicated that age ≥ 65 years, CA19-9 ≥ 1,000 U/ml and positive S100A11 were independent prognostic indicators of pancreatic adenocarcinoma (P = 0.002, 0.004 and 0.001, respectively). These results suggested that S100A11 might be a significant tumor marker for pancreatic adenocarcinoma and an unfavorable predictor for prognosis of patients who have undergone surgical resection.