The purpose of this study was to evaluate the expression of PAD4 in nasopharyngeal carcinoma and to explore the relationship between PAD4 and the basic characteristics of 5-8F cells. Immunohistochemistry was used to evaluate the overexpression of the PAD4 protein in the nasopharyngeal carcinoma tissue of 30 patients diagnosed by biopsy in the Third Affiliated Hospital of Guangxi Medical University from January 2018 to June 2019. At the same time, cell function in vitro was evaluated in 5-8F cell line. Cell proliferation, apoptosis and cell cycle were analysed using the MTT assay and flow cytometry. Reverse transcription quantitative polymerase chain reaction was used to evaluate the ability of invasion and angiogenesis. The expression level of PAD4 was related to the size and stage of the primary tumour, lymph node status and pathological grade. Compared to the control group, the activity of PAD4 knockdown cells decreased significantly, the number of the apoptotic cells and the percentage of cells in G0/G1 phase in the PAD4 siRNA group were significantly higher than that in the control group. The invasion and angiogenic ability of 5-8F cells in PAD4 siRNA group were significantly lower than that in the control group. PAD4 was overexpressed in nasopharyngeal carcinoma, which was related to its poor clinicopathological features. At the same time, silencing PAD4 can inhibit the proliferation and activity of 5-8F cell lines, which may provide a potential therapeutic target for patients with nasopharyngeal carcinoma.