Abstract: Objective To observe the effects of high mobility group box-1 protein (HMGB1) on the migration and invasion ability of human nasopharyngeal carcinoma(NPC) cell line-C666-1 in vitro and to preliminarily explore its potential mechanism. Methods The HMGB1 expression in NPC cell line C666-1 was down-regulated by siRNA. The cell migration and invasion ability were detected by scratch test and Transwell. Invasion-related protein MMP2 and MMP9 expression in these cells were detected by Western blot. Results Compared with the control group, the cells migration and invasion ability and MMP2 expression were obviously decreased in siHMGB1 group (all P<0.001), but MMP9 expression was not changed obviously. Conclusion HMGB1 promotes the migration and invasion ability of human NPC cell line C666-1 in vitro, and the effect on invasion ability may be via regulating MMP2 expression.