Abstract: Objective To investigate the effects of cisplatin induction in vitro on human nasopharyngeal carcinoma cells CNE2 and its possible molecular mechanism. Methods Proliferation of CNE2 cells treated with various concentrations(0.4-4.0 mg/L) of cisplatin was determined using MTT assay. The senescent cells were determined by a senescence-associated-β-galactosidase(SA-β-gal) activity assay and cell cycle distribution was analyzed by flow cytometry. A Sybe Green real-time polymerase chain reaction(RT-PCR) method was used to examine the changes of expression profiles of 78 human cellular senescence-related genes. Results Cisplatin inhibited the proliferation of CNE2 cells in a dose- and time-dependent manner, and significantly induced a cellular senescence in CNE2 cells, which respectively counted at 67.63% of senescent cells at day 6 and 89.22% at day 8, after treatment with 1.0 mg/L of cisplatin. A G2/M phase arrest was observed. The expression levels of 16 senescence-related genes including TP53, TP63, p16Ink4a, p27Kip1, PTEN, RB1, TBX3, Cdc25C, Gadd45a, IGF1R, PIK3CA, MI-1, B2M, MORC3, MYC and SPARC were increased(P＜0.05 or 0.01), while the 14 genes including Cyclin A2, Cyclin B1, Cyclin E1,CDK6, ATM, E2F1, ETS1, ETS2, MDM2, FN1, IGFBP3, RBL2, SERPINB2 and SIRT1 were decreased at mRNA levels(P＜0.05 or 0.01). Conclusion Cisplatin could induce G2/M phase arrest and cellular senescence in CNE2 cells in vitro, which may involve a omplicated network of p53-pRb signaling or/and PTEN signaling pathways mediated by p16 and p27.