Previous studies have demonstrated that Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) in combination chemotherapy functions through mannose-modified proteins to inhibit cancer cell proliferation, induce apoptosis, and promote an anti-tumor immune response. PA-MSHA also has displayed anti-tumor activity in breast, liver, lung, gastric, and bladder cancer [10–12]. EGFR overexpression and/or enhanced activity has been reported in many solid tumors including pancreatic cancer . Activation of EGFR results in phosphorylation and activation of downstream signaling components and leads to cell proliferation . In this study, we investigated the mechanisms underlying PA-MSHA function. We assessed whether PA-MSHA induced apoptosis in pancreatic cancer cells, and evaluated the association between PA-MSHA-mediated anti-tumor effects and EGFR signaling. Additionally, we evaluated the therapeutic potential of PA-MSHA.