Moreover, we explored the molecular pathways involved in 5‐FU resistance induced by miR‐21 and found that miR‐21‐induced 5‐FU resistance in pancreatic cancer mainly depends on the down‐regulation of its two tumor suppressor targets, PTEN and PDCD4. We also demonstrated the inhibitory role of PTEN and PDCD4 in 5‐FU resistance in pancreatic cancer cells. The gene discussed is PDCD4; the disease is familial pancreatic carcinoma.