Introduction: A systematic review and meta-analysis was conducted to assess the efficacy and safety of iodine-125 implantation combined with gemcitabine in the treatment of advanced pancreatic cancer. Methods: PubMed, Chinese National Knowledge Infrastructure database (CNKI), Cochrane Library, Embase, and Wanfang database through Oct 2020 were searched for randomized controlled trials (RCTs) and retrospective studies assessing the efficacy and safety of iodine-125 implantation combined with gemcitabine in the treatment of advanced pancreatic cancer. The main outcome measures included the overall remission [complete response (CR)+partial response (PR)] rate, overall survival (OS), hypofunction of the liver, clinical benefit response (CBR) rate, survival rate, and adverse events. Results: Totally, 19 studies involving 1496 patients were included in the current systematic review and meta-analysis. The pooled results showed that efficacy and safety of patients treated with Iodine-125 combined with gemcitabine were superior to those undergoing gemcitabine alone: overall remission (CR+PR) rate [odds ratio (OR)=3.