Abstract: Objective:To compare the clinical effects and adverse reactions of high intensity focused ultrasound (HIFU) and gamma knife radiotherapy for treatment of advanced pancreatic carcinoma. Methods:Eighty patients with advanced pancreatic carcinoma were divided into 2 groups. Group A ( n=26) patients underwent HIFU. In Group B ( n=54), patients re -ceived gamma knife radiotherapy. The treatment effects including the rates of local control, mean survival time, clinical ben-efit response (CBR) and the frequency of complication in the 2 groups were compared. CBR was defined as a≥50% re-duction in pain intensity, ≥50% reduction in daily analgesic consumption, or≥20point improvement in KPS that lasted for ≥4 consecutive weeks. The tumor response rate was evaluated by RECIST. Results:Average survival period was 5.6 ± 4.1 and 5.4 ± 3.6 months, respectively. The rates of local control in the2 groups were 26.9% and 24.1%, respectively. No sig-nificant statistical differences were shown (P=0.962 ). The CBR was 84.6% in Group A, and 57.4% in Group B, which showed a significant difference between the 2 groups (P= 0.022 ). The major adverse reactions were: bone marrow suppres -sion, nausea, vomiting. The rates of complication in group A were distinctly lower than those in Group B (P=0.040 ). Conclusion: HIFU and gamma knife radiotherapy were both noninvasive, safe, and effective palliative therapy methods for ad-vanced pancreatic cancer. The overall response rates and average survival periods were similar. But HIFU therapy was su-perior to gamma knife radiotherapy in pain alleviation. As well, there was less injury, less bone marrow depression and less nausea and vomiting in HIFU therapy group. HIFU was adaptable for the patients who were in bad general condition, who couldn ’t tolerate the gamma knife radiotherapy.