This study aimed to analyze the expression, clinical significance of proto-oncogene in nasopharyngeal carcinoma and the biological effect in its cell line by siRNA targeting wild-type p53-induced phosphatase 1 (Wip1). Immunohistochemistry and western blot were respectively used to analyze Wip1 protein expression in 85 cases of nasopharyngeal cancer and normal tissues to study the relationship between Wip1 expression and clinical factors. Wip1 siRNA was transiently transfected into papillary nasopharyngeal carcinoma cell by liposome-mediated method and was detected by Quantitative real-time RT-PCR (qRT-PCR) and western blot. MTT assay, cell apoptosis, migration and invasion were also conducted as to the influence of the down-regulated expression of Wip1 that might be found on CNE2 cells biological effect. The level of Wip1 protein expression was found to be significantly higher in nasopharyngeal cancer tissue than normal tissues (P < 0.05). There were significant differences between Wip1 expression and T stages, lymph node metastasis, clinical stages, tumor differentiation and radiotherapy response (P < 0.05), regardless of age, gender (P > 0.05). Meanwhile, Increased expression of Wip1 was significantly with poor overall survival time by Kaplan-Meier analysis (P < 0.05). Wip1 expression deletion determines independent risk factors for prognosis of patients with nasopharyngeal carcinoma in addition to tumor T stage, clinical stage, histological grade and lymph node metastasis outside by Cox-2 in the regression analysis (P < 0.05). qRT-PCR and Western blot showed that CNE2 cell transfected Wip1 siRNA had a lower relative expressive content than normal cell (P < 0.05). MTT assay, cell apoptosis, cell cycles demonstrated that CNE2 cell transfected Wip1 siRNA had a lower survival fraction, higher cell apoptosis, more percentage of the G0/G1 phases, significant decrease in migration and invasion, and higher P53 and P16 protein expression compared with CNE2 cell untransfected Wip1 siRNA (P < 0.05). Wip1 protein was increased in nasopharyngeal carcinoma, specifically in T stages, lymph node metastasis, clinical stages and tumor differentiation. Wip1 may involved in the biological processes of nasopharyngeal cancer cell proliferation, apoptosis, and migration and invasion by regulation P53 and P16 protein expression.