The pathogenesis, early diagnosis, and treatment of pancreatic cancer have always been a hot and important topic of concern in the medical community. In recent years, a number of studies have shown that epigenetics plays an important role in the occurrence and development of tumors, with DNA methylation being the most common form. The development of pancreatic cancer is related to the abnormal activation or inhibition of its related oncogenes or tumor suppressor genes due to changes in DNA methylation levels. DNA methylation may occur before somatic cell mutations and runs through the entire process of tumor development, and therefore, it has been widely studied in the diagnosis, treatment, and prevention of tumors. In this article, the authors provide an overview of the concept and mode of action of DNA methylation, its role in the initiation and progression of pancreatic cancer, and its prospects in the diagnosis and treatment of pancreatic cancer, in order to provide a reference for future research on pancreatic cancer.