ObjectiveTo explore the mechanisms of perineural invasion (PNI) in pancreatic cancer so as to find a new treatment for pancreatic cancer. MethodsThe literatures on PNI, neurotropism, nerve-tumor microenvironment and nerve growth factor in pancreatic cancer were reviewed and the mechanisms of PNI were summarized. ResultsThe rich innervation of pancreatic tissue itself and the minute slits within perineural structure were the anatomic basis of PNI. Tumor cells expressed neural antigens were the pathological basis of PNI. Tumor-nerve microenvironment and nerve growth factor family and themselves receptors might play an important molecular role in PNI. However, tumor cells expressed neural antigens were not only closely related to the PNI, but also the interaction between tumor cells and nerves played an important role in PNI. ConclusionsThe detailed mechanisms of PNI are extremely complex and controversial up to today. However, it is possible to search a new therapeutic target in pancreatic cancer according to the mechanisms of PNI.