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This study aimed to analyze the clinical safety and effectiveness of endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in alleviating intractable abdominal pain caused by advanced pancreatic cancer. A total of 58 patients with inoperable pancreatic cancer who underwent EUS-CPN from May 2015 to December 2017 were enrolled. Pain levels before and after EUS-CPN were assessed and compared using the Visual Analogue Scale. The preoperative Visual Analogue Scale score was 8.2±2.3, which decreased significantly to 3.6±1.5 at 2 days after EUS-CPN and to 2.2±0.8 after 1 month. The response rate was 79.3%. No patient experienced serious complications; 14 patients experienced mild, transient side effects (self-limiting diarrhea, reflex hypotension, and worsening of abdominal pain) that resolved within 48 hours. For pancreatic cancer patients, EUS-CPN can effectively control pain with minimal adverse effects.