Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca(2+) current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca(2+) current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.