Nasopharyngeal Carcinoma (NPC) is the most common cancer originating in the nasopharynx. Aberrant proliferative signals and apoptotic dysregulation are required for NPC development. However, the mechanisms behind them are still unclear. In this study, we explored role of GON4L, a new-found transcriptional repressor, in NPC cells. Knockdown of GON4L expression impaired NPC cells colony formation and proliferation. Cisplatin-induced apoptosis was enhanced by downregulation of GON4L. Forced expression of GON4L resulted in promoted proliferation and inhibited apoptosis of NPC cells induced by Cisplatin. Furthermore, GON4L knockdown inhibited β-catenin accumulation, wnt, P53 and Bcl-2 expression. Inhibition of GON4L transcriptional suppressive activity reversed GON4L-induced NPC cells proliferation and survival. In conclusion, these data suggest that oncogenic role of GON4L and provide a new potential therapeutic target for NPC treatment.