Objective: To study therapeutic effect and safety of high intensity focused ultrasound (HIFU) combined Gemcitabine on unresectable pancreatic carcinoma (PC). Methods: Total 45 PC patients were randomly divided into 2 groups: experimental group (treating with HIFUT and gemcitabine, n=23), control group (treating with gemcitabine only, n=22). The therapeutic effects and clinical benefit rates in two groups were compared by using the Kaplan-Meier and Log-Rank tests, including the median survival time (MST), 6-month and 12-month survival rates. Results: Our results showed that MST and 6-month survival rates of experimental patients were significantly higher than that of control patients (8.91 vs 5.53 mths, 73.9 vs 40.9%, p<0.05). For the 12-month survival rates, no statistically difference was observed between the two groups (13.0 vs 4.5%, p>0.05). The clinical benefit rates in experimental group and control group were 69.6% and 36.3%, respectively (p<0.05). The pain remission rate in experimental group was significantly higher than in control group (65.2 vs. 31.8%, p<0.05). Conclusions: For treating pancreatic carcinoma, HIFUT combined gemcitabine is better than gemcitabine only. The former treatment (HIFUT combined gemcitabine) may become a better effective treatment strategy for treating unresectable pancreatic carcinoma.