BACKGROUND AND OBJECTIVES: Currently, extended resection and preoperative neoadjuvant chemotherapy are the two main modalities for improvement of the resection rate and R0 resection rate of borderline resectable pancreatic cancer. The past few years, however, have witnessed some progress in the treatment of unresectable pancreatic cancer with high intensity focused ultrasound (HIFU). The aim of this study is twofold: first, to evaluate the feasibility and safety of HIFU ablation as a preoperative adjuvant therapy for borderline resectable pancreatic cancer, and second, to conduct pathological analyses to verify the safety and effectiveness of HIFU treatment of pancreatic cancer. METHODS: From January 2011 to December 2012, 30 patients with borderline resectable pancreatic cancer underwent HIFU ablation by Haifu Model-JC200 Focused Ultrasound Tumor Therapeutic System prior to radical surgery. The effect of pre-operative HIFU ablation was evaluated by post-HIFU functional imaging results, operation time of radical surgery, blood loss volume, R0 resection rate, postoperative 1-year survival rate and Ca199 curve. Postoperative pathological specimens were obtained for histological examination. RESULTS: All 30 patients with borderline resectable pancreatic cancer had completed the treatments and follow-ups. Functional image assessment after HIFU treatment showed a mean tumor ablation rate of (61.5±24.3)%. 28 patients underwent radical resection of pancreatic cancer 7-9 days after HIFU treatment (23 cases underwent pancreaticoduodenectomy. 4 patients underwent pancreatectomy and 1 patient had total pancreatectomy). 7 patients underwent combined resection and reconstruction of portal-superior mesenteric vein (23.3%), with the resectability rate of 93.3%, the R0 resection rate of 92.7%, and the 1-year survival rate of 96.7%. The biological coagulative necrosis regions identified by the postoperative pathological examination matched well with the necrosis foci identified by post-operative functional imaging. CONCLUSION: The effectiveness of HIFU ablation of pancreatic tumors, as well as interstitial tissues within he main vascular spaces was confirmed by post-operative pathological examinations. Based on these observations, we conclude that preoperative HIFU ablation of borderline resectable pancreatic cancer can significantly improve the resection rate, R0 resection rate, and reduce the difficulty and risk of surgery. Therefore, HIFU may be a valuable pre-operative adjunct therapy for resectable pancreatic cancer. However, the safety and the efficacy on the improvement of the surgery need to established with future multicenter, randomized studies.