In the present study, we demonstrate for the first time that ANXA2 upregulates the transcriptional activity of NF-κB by binding to and facilitating nuclear translocation of the p50 subunit of NF-κB. In addition, overexpression of ANXA2 is linked to gemcitabine resistance in pancreatic carcinoma through NF-κB-dependent expression of several anti-apoptotic genes. Here, NFKB1 is linked to exocrine pancreatic carcinoma.