LPLUNC1 is a newly cloned gene and was found down-expressed in 71% NPC biopsies but high-expressed in normal adult and fetal nasopharyngeal epithelial tissue, which indicates that it may play an important role in the tumorigenesis of nasopharyngeal carcinoma. The object of the research is to study the effect of LPLUNC1 on nasopharyngeal carcinoma cells. The full length of LPLUNC1 cDNA was cloned into the pcDNA3.1(+) vector, then the pcDNA3.1(+)-LPLUNC1 plasmid was stably transfected into the NPC cell line HNE1 cells using lipofectamine. After being selected with G418 and detected with RT-PCR and Northern-blot, the stable transfectants of LPLUNC1 over-expression were constructed. Cell growth curve, MTT, BrdU labeling, flow cytometry, soft agar and nude mice were performed to study the effects of LPLUNC1 over-expression on HNE1 cells. The results showed that HNE1 cells with over-expression of LPLUNC1 grew slower significantly than that of the control. MTT and BrdU labeling assay showed that LPLUNC1 inhibited the HNE1 cell proliferation. And LPLUNC1 gene can delay G1-S phase cell cycle progression of HNE1 cells. Furthermore, LPLUNC1 was found that it decreased the HNE1 clonogenicity in soft agar and inhibited the tumor formation in nude mice obviously. In conclusion, LPLUNC1 can suppress the malignant phenotype of HNE1 and plays an important role in inhibiting the tumorigenesis and development of NPC.