Vemurafenib and trametinib have a lot of successful experiences in the treatment of unresectable or metastatic melanoma with BRAF V600E mutation. However, they have not been reported in the treatment of advanced pancreatic ductal adenocarcinoma (PDAC). We report here a 66-year-old male who was diagnosed as PDAC with multiple metastases of the abdominal cavity and liver according to pathological examination. After three cycles of gemcitabine plus nab-paclitaxel (GA) regimen chemotherapy, the liver metastasis of the patient progressed, and the patient could not continue to receive chemotherapy because of poor physical condition. BRAF V600E mutation was found by genetic detection in this patient, so targeted therapy with vemurafenib combined with trametinib was performed and the follow-up period was up to 24 months. To the best of our knowledge, this is a rare report that patients with stage IV PDAC with BRAF V600E mutation can receive significantly survival benefits from targeted therapy with vemurafenib combined with trametinib. This report provides experience for the use of these two drugs in patients with advanced PDAC.