Immunotherapy has been recommended as a second-line treatment only for high microsatellite instability or DNA mismatch repair deficiency advanced pancreatic cancer in National Comprehensive Cancer Network guidelines. Here, we report a case with a good response to immunotherapy in pancreatic cancer with mismatch repair proficiency. A 55-year-old woman diagnosed with pancreatic cancer cT4N1M1 (liver, lung) who harbored ERBB2 mutations with high tumor mutation burden (TMB) underwent multiple therapies and survived 19 months. A partial response in pancreatic cancer was observed when the patient was treated with combined antiangiogenic therapy and immunotherapy after a series of ineffective treatments. Neutrophil-to-lymphocyte ratio (NLR), a predictive marker of efficacy of immunotherapy, confirmed that immunotherapy resulted in the partial response in pancreatic cancer. To our knowledge, this is the first to report advanced pancreatic cancer with mismatch repair proficiency had a good response to immunotherapy, and this is the first to report an association between high blood-based TMB or NLR and improved clinical outcomes in pancreatic cancer. Therefore, TMB may also be a biomarker for immunotherapy of pancreatic cancer, and NLR may be a prospective predictive marker for efficacy of immunotherapy in pancreatic cancer.