Pancreatic cancer is a major cause of cancer-related mortality around the world. Currently, options for diagnosis and treatment are extremely limited, which culminates in a very high mortality rate. Intensive research spanning more than four decades has met several roadblocks in terms of improvement in overall survival. In this study, we have evaluated the effect of Hydroxychavicol (HC), a naturally occurring and abundantly isolatable allylarene from Piper betle leaves on pancreatic cancer cells. Our investigation reveals that HC inhibits proliferation and epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. HC induces DNA damage, as evidenced by γ-H2AX, 53BP1 induction and comet assay, which further results in mitotic catastrophe and apoptosis. The apoptosis induced by HC is JNK pathway-dependent and caspase-mediated. HC also inhibits migration and invasion of pancreatic cancer cells via a generalized repression of genes involved in EMT. A quantitative real time PCR-based array revealed at least 14 different genes to be differentially expressed upon HC treatment in pancreatic cancer cells. These results show significant potential of HC as an anticancer agent against pancreatic cancer.