Abstract： Objective To investigate the clinical benefit response (CBR) in treating the unresectable pancreatic carcinoma by applying the EUS guided iodine-125 seed implantation combined with chemotherapy of gemeitabine and comparing chemotherapy of gemcitabine alone. Methods Forty-one patients with unresectable pancreatic carcinoma were randomly divided into two groups, one group (Group A) included 21 cases which underwent EUS-guided iodine-125 seed implantation combined with gemcitabine chemotherapy, the rest 20 cases (Group B) were treated with gemcitabine chemotherapy alone. EUS-guided iodine-125 seed implantation were carried according to the treatment plan system (TPS), following chemotherapy after 1 week. Gemcitabine was administered at the dose of 1 000 mg/m2, through intravenous administration once a week for 3 consecutive weeks every 4 weeks. CBR was assessed. Results CBR of Group A was 57.1% and median time to CBR was 1 week and median duration of CBR was 21 weeks, while CBR of Group B was 25%, and median time to CBR was 4 weeks and median duration of CBR was 15 weeks (P<0.01). Conclusions EUS-guided iodine-125 seed implantation combined with chemotherapy of gemcitabine was superior to gemcitabine chemotherapy alone in the term of CBR in patients with unresectable pancreatic carcinoma.