LTF (lactotransferrin, or lactoferrin) plays important role in innate immunity, and its anti-tumor function has also been reported in multiple cancers. We previously reported that LTF is significantly down-regulated in nasopharyngeal carcinoma (NPC) and acts as a tumor suppressor by suppressing AKT signaling. However, the exact mechanism of the down-regulation of LTF in NPC has not been revealed. In the current study, we screened and identified LTF is a bona fide target of miR-214 in NPC cells. miR-214 mimics significantly suppressed LTF mRNA and protein expression levels in NPC cells. miR-214 not only can promote NPC cell proliferation and invasion abilities in vitro, but also can accelerate tumor formation and lung metastasis in a mouse xenograft model. The pro-tumor function of miR-214 was depended on LTF suppression since LTF re-expression can reverse it. miR-214 can also activate AKT signaling by suppressing LTF expression. Furthermore, miR-214 expression level was up-regulated in NPC especially in metastasis-prone NPC tumor tissues compared with normal nasopharyngeal epithelial tissues, while the LTF expression level was negatively correlated with miR-214, suggesting that miR-214 targeting is partly responsible for LTF down-regulation in NPC specimens.