Abstract: Objective To investigate the application of cone-beam computed tomography （CBCT） and ultrasonic technology guided high intensity focused ultrasound （HIFU） combined with intensity modulated radiation therapy （IMRT） for pancreatic cancer. Methods The method of HIFU combined IMRT was used on 21 pancreatic cancer patients collected from December 2010 to June 2012. The treatment effect of HIFU was assessed through the doppler ultrasound， the treatment doses and times of next fraction were regulated according to patient tolerance， the tumor and its blood supply. CBCT guided IMRT was executed with a total dose from 58Gy to 70Gy， and 2Gy at one time， 5 fractions a week， lasting for 6-7 weeks. The setup error and PTV boundary after CBCT guided IMRT were analyzed.The pain relief effect and KPS score were evaluated. Results The total fractions of HIFU were 6-18. The IMRT treatment precision was less than 2mm on average with CBCT guiding. Twelve patients'pain all alleviated completely； 8 patients' pain alleviated partially and 1 case was invalid. There was no serious complication occurred with a total efficacy of 95.0％ in 21 patients. The KPS score of patients before treatment was 46.8±9.1, which was lower than that after treatment（87.1±8.3）, showing significant differences（P＜0.05）. Three patients died， and the average survival time was 10 months. Conclusion With a substantial increase in treatment precision， the combination of HIFU and IMRT enhanced the tumor control ability，deceases the dose of organs at risk to a safe value，and the complications are reduced with improved living quality of patients.