Pancreatic cancer is a clinically challenging disease with a poor survival rate and is one of the leading causes of cancer-related morbidity. It is highly resistant to treatment and effective diagnostic tools during the early stages of the disease are lacking. Long non-coding RNAs (lncRNAs) participate extensively in the physiological processes of various diseases, especially multiple types of cancers. lncRNAs have been shown to perform essential functions and are gaining increasing attention in pancreatic cancer research. This review summarizes the roles of lncRNAs in the occurrence, development, and therapeutic resistance of pancreatic cancer by categorizing their regulation of epigenetic inheritance, transcription, post-transcription, and related signaling pathways. Potential clinical implications, including diagnostic and prognostic biomarkers, as well as the therapeutic prospects of these lncRNAs in pancreatic cancer, are also discussed. Novel insights into the role of lncRNAs in the pathogenesis of pancreatic cancer may help researchers develop novel therapeutic strategies. This review summarizes the roles of long non-coding RNAs (lncRNAs) in occurrence, development, and therapeutic resistance of pancreatic cancer by categorizing regulation of epigenetic inheritance, transcription, post-transcription, and related signaling pathways. It also discuss the potential clinical implications, including diagnostic and prognostic biomarkers, as well as therapeutic prospects and adverse effects of gene therapy targeting lncRNAs in pancreatic cancer.image