Objective: To investigate the expression of human phosphatidylethanolamine-binding protein 4 (hPEBP-4) in pancreatic cancer tissue and its clinical significance. Methods: The mRNA and protein expressions of hPEBP-4 in specimens of pancreatic cancer and paired adjacent tissues from 30 patients were determined by qRT-PCR, Western blot and immunohistochemical staining, respectively. The relations of the hPEBP-4 expression with clinicopathologic variables and prognosis of the pancreatic cancer patients were analyzed. Results: The results of qPCR and Western blot showed that the mRNA and protein expressions of hPEBP-4 were obviously up-regulated in 24 specimens of the 30 pancreatic cancer tissues relative to their adjacent tissues. The results of immunohistochemical staining showed that the high expression rate of hPEBP-4 in pancreatic cancer tissues was significantly higher than that in adjacent tissues (80.0% vs. 16.7%, χ2=24.093, P<0.001). The expression level of hPEBP-4 was significantly related to the degree of tumor differentiation, serum CA19-9 level and TNM stage (all P<0.05). The results of correlation analysis showed that the differentiation degree of pancreatic cancer and TNM staging were negatively correlated with hPEBP-4 (r=–0.507, P=0.004; r=–0.400, P=0.028), while serum CA19-9 level was positively correlated with hPEBP-4 (r=0.428, P=0.018). The results of survival analysis showed that the overall survival rate in patients with low hPEBP-4 expression was significantly higher than that in patients with high hPEBP-4 expression (χ2=8.658, P=0.003). Conclusion: The expression of hPEBP-4 is increased in pancreatic cancer tissue, which is associated with some malignant pathological features and poor prognosis in pancreatic cancer.