Pancreatic cancer is one of the most lethal malignancies in the world, and has an extremely poor prognosis. Because of the non-specific symptoms with insidious onset and rapid development, most patients are diagnosed at an advanced stage, which deprives them of adequate treatment opportunities. At present, most patients with pancreatic cancer are diagnosed by imaging examination, biochemical examination and tissue biopsy. Each of the existing methods has its own imperfections. In recent years, with the deepening research on tumor mechanism and the development of liquid biopsy technology, circulating tumor DNA (ctDNA) has gradually attracted extensive attention and played an increasingly important role. In this review, the authors describe the clinical application of ctDNA in pancreatic cancer in terms of early diagnosis, prognosis evaluation, chemotherapy efficacy, and targeted therapy.