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A line of studies has demonstrated that EMT phenotype is closely related with tumor progression and drug resistance in a variety of human cancers.Recently, it has been extensively demonstrated that microRNAs (miRNAs) play a pivotal role in regulating EMT.In our previously reports, we have reported that inhibition of miR-223 could reverse EMT phenotype and improve chemotherapeutic drug sensitivity and genistein down-regulated miR-223 expression in pancreatic gemcitabine-resistant (GR) cells.Here, we explored whether there was the synergy between miR-223 inhibitor and genistein on cell growth, migration, invasion and reversal of EMT in pancreatic GR cells.We found that the combination of miR-223 inhibitor and genistein synergistically reduced cell motility and invasion and enhanced gemcitabine sensitivity in pancreatic GR cells.In addition, we further observed that miR-223 inhibitor and genistein reversed EMT features in pancreatic GR cells.This study suggests that the combination of miR-223 inhibitor and genistein may be a potential therapeutic strategy for the treatment of pancreatic cancer.