To the best of our knowledge, this report is the first to provide insight into lncRNA-mediated epigenetic crosstalk between CAFs and pancreatic cancer cells to mediate oxaliplatin resistance, and our findings emphasize that the IL8/UPK1A-AS1 axis may constitute a novel therapeutic target for overcoming platinum resistance in pancreatic cancer patients. This evidence concerns the gene CXCL8 and familial pancreatic carcinoma.