A 52-year-old man was diagnosed with small bowel adenocarcinoma(T4aN1M0, Stage ⅢA, according to the Japanese colorectal cancer classification)and treated with partial resection of the small bowel in June 2014. He also received adjuvant chemotherapy(XELOX: 8 courses)after surgery. Three and a half years after the operation, peritoneal dissemination recurred, and he received bevacizumab plus XELOX therapy. The regimen was adjusted to a total of 11 courses because of the disease progression. The primary lesion showed MSI-H. The patient was started on pembrolizumab therapy in April 2019. The tumor responded well to pembrolizumab(maximum therapeutic effect: PR, 31% reduction), but a new lesion appeared 6 months after the start of this regimen. He continued pembrolizumab therapy for 14 months without adverse events since it appeared to be clinically effective. Although MSI-H small bowel cancers are rare, accurate screening is essential to not miss the opportunity to administer pembrolizumab.