Oxidored-nitro domain containing protein 1 (NOR1) is a candidate tumor suppressor gene that is down-regulated in nasopharyngeal carcinoma (NPC). In the present study, NOR1 stable transfected NPC 5-8F cells were established. As a result, the 5-8F cells expressing NOR1 showed dramatic morphological changes comparing with the control, such as less lamellipodia protrusions and membrane ruffles at the periphery of the cells. Ectopic expression of NOR1 in NPC 5-8F cells also inhibited microvillus formation on the surface of tumor cells due to filamentous actin rearrangement. Further more, realtime RT-PCR assay revealed that ectopic expression of NOR1 suppressed the expression level of FZD5 and FZD7, and then attenuated β-catenin nuclear translocation. This first report provides experimental proof to probe the function of NOR1 gene in the process of lamellipodia formation and the Wnt signaling in NPC cells.