In this study, we identify that miR-320a plays an important role in promoting 5-FU resistance of human pancreatic cancer cells by targeting PDCD4, and facilitating several aspects of pancreatic cancer pathogenesis, including proliferation, invasion, metastasis, drug-resistance characteristics and the epithelial-to-mesenchymal transition. The gene discussed is PDCD4; the disease is familial pancreatic carcinoma.