Abstract: Objective To demonstrate the effects of apoptosis-inducing and proliferation-inhibiting of zoledronic acid (ZOL) in human nasopharyngeal carcinoma cell HNE-1 and explore its potential mechanism. Methods The ability of cell proliferation was detected by MTT assay. Cell apoptosis and cycle were analyzed by fl ow cytometry. DNA fragmentation of apoptotic cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay. The expression of mRNA and protein of apoptosis-related genes, such as Bcl-2, Bad, Bax and Caspase-9, were investigated by Real-time PCR and Western blot. Results Compared with control group, different concentrations of ZOL(2.5, 5, 10, 20, 40 μmol/L) did not show an inhibition effect on the proliferation of HNE-1 cells at the time point of 24 h by MTT assay. While the anti-proliferative effect was found obviously over a period of incubation of 48 h as well as 72 h(P<0.05), but not shown in a doseor time-dependent manner(P>0.05). The rate of early apoptosis was signifi cantly higher than that of control group over an incubation time of 48 and 72 h. After incubated with ZOL for 48 h, HNE-1 cells showed a cell cycle arrest in S phases. TUNEL method showed more apoptotic cells in the experiment group (P<0.05). Realtime PCR and Western blot revealed that the proapoptotic genes, Bad, Bax, and Caspase-9, were up-regulated in ZOL-treated HNE-1 cells, whereas the antiapoptotic gene Bcl-2 was down-regulated both in mRNA and protein levels. Conclusion ZOL could inhibit cell proliferation and induce cell apoptosis in HNE-1 cells, which might be related with down-regulating protein expressions of antiapoptotic Bcl-2 gene and upregulating proapoptotic genes, Bax, Bad and Caspase-9.