The objective of this study was to investigate the expression and clinical relevance of interleukin 22 (IL-22) and IL-22-producing CD4 T cells (IL-22CD4 T cells) in pancreatic cancer (PC) tissues.Interleukin 22 protein levels in PC tissues were measured by Western blot analysis and immunohistochemistry. The frequencies of IL-22CD4 T cells in tumors and peripheral blood from PC patients and control subjects were analyzed by flow cytometry. The association between IL-22 and phosphorylation of STAT-3 was investigated in in vitro model.Interleukin 22 protein was more highly expressed in PC tissues than in peritumoral and normal pancreatic tissues. The frequencies of all IL-22CD4 T cells and T helper 22 (TH22) cells (IL-22IFN-γIL-17CD4) were significantly higher in PC tissues than in the peripheral blood of PC patients and control subjects. It was observed that up-regulation pSTAT-3 and its downstream genes such as Bcl-2 and cyclin D1 in vitro. Finally, we found that increased intratumoral IL-22 expression and frequencies of TH22 and IL-22CD4 T cells were positively correlated with PC tumor-node-metastasis staging.Increased intratumoral IL-22 levels, IL-22CD4 T cells, and TH22 cells are correlated with PC tumor-node-metastasis staging, suggesting that IL-22 and IL-22CD4 T cells may be related to tumor progression and are potential therapeutic targets in patients with PC.