Precision medicine is a novel medical concept and model, which developed from the base of personalized medicine, and with the rapid progress of genome sequencing technology and cross penetration of bioinformatics and big data science, and has increasingly shown its value in clinical treatment of malignant tumors. Over the recent years, the surgical techniques in pancreatic surgery has become more mature, along with the rapid development in a range of disciplines such as imaging technology, surgical instruments, energy platform, adjuvant therapies and targeted drugs, which provide a foundation and possibility for the treatment of pancreatic cancer, one of the most lethal solid malignant tumors, stepping into individualized stage. Circulating tumor DNA (ctDNA) bears the genetic characteristics of the tumors, and in this article, the authors address the clinical significance of ctDNA mutation detection in precision development direction of diagnosis and treatment of pancreatic cancer.