The long non-coding RNA (lncRNA) H19 has been recently shown to participate in the progression of cancer, including metastasis. However, the biological role of H19 and the underlying mechanisms mediating its functions in nasopharyngeal carcinoma (NPC) remain unclear. Herein, we found that H19 was overexpressed in NPC tissues and poorly differentiated cell lines. Knockdown of H19 significantly inhibited the invasive ability of NPC cells. Moreover, H19 affected the expression of enhancer of zeste homolog 2 (EZH2), which has also been observed to be up-regulated in NPC and to promote cell invasion. Rather than direct interaction, H19 regulated EZH2 expression by suppressing the activity of miR-630, which is a repressor of EZH2 and interacts with H19 in a sequence-specific manner. Furthermore, H19 inhibited E-cadherin expression and promoted cell invasion of NPC cells via the miR-630/EZH2 pathway. Our data suggest an important role for H19 in NPC metastasis and suggest the feasibility of therapy for NPC involving modulation of the novel regulatory network.