Overexpression of XIST significantly promoted the proliferation,migration and invasion, and suppressed cell apoptosis of BxPC-3 cells; knockdown of XIST significantly inhibited the proliferation,migration and invasion,and accelerated cell apoptosis of PANC-1 cells. Subsequently, we found that microRNA-34a-5p (miR-34a-5p) was downregulated in PC tissues,and predicted a poor prognosis in PC patients. In addition, the results indicated that miR-34a-5p is a target gene of XIST and was significantly negatively correlated with XIST. More importantly, miR-34a-5p rescued the facilitation of malignant behavior mediated by XIST. These results indicated that XIST and miR-34a-5p may be potential effective therapeutic targets for PC.