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Human leucocyte antigen G (HLA-G) was shown to be associated with immune suppression and unfavorable prognosis in multiple types of cancers. However, its expression in pancreatic cancer (PC) was less investigated. Particularly, its roles in PC remain unknown. The present study aimed to address the issues. Expression of HLA-G was detected by Western blot and tissue microarray-based immunohistochemical staining in 10 and 158 patients with PC, respectively. In addition, tumor infiltrating lymphocytes (TIL) labeled by CD3 staining, as a marker of host immune response, were counted. Finally, immunohistochemical HLA-G expression was linked to clinicopathologic variables, TIL number and overall survival. It was found that HLA-G was overexpressed in 4 out of 10 patients. For staining, HLA-G expression was much higher in tumor than in non-tumor tissues. Tumoral expression of HLA-G was closely associated with T stage. Intratumoral CD3-positive TIL in tumors with diffuse HLA-G expression was less than that in those with negative or local HLA-G expression, but no significant differences for stromal TIL were observed. Univariate analysis found that diffuse HLA-G expression in tumor tissues and low intratumoral CD3-positive TIL number were of predictive significance for poor overall survival of PC. Furthermore, HLA-G expression and intratumoral CD3-positive TIL number were identified, by multivariate Cox regression test, as independent prognostic factors. Our data suggest that HLA-G impairs host immune response and predicts poor prognosis in PC.