The significance of SOX2 in nasopharyngeal carcinoma (NPC), a tumor associated with Epstein-Barr virus (EBV), remains unclear. Here, we reported that, in the univariate analysis, SOX2 expression was correlated with a poorer distant metastasis-free survival (DMFS). The EBV-VCA/IgA titers in patients with NPC were also associated with a poorer overall survival (OS). Patients with NPC, who had both strong staining of SOX2 and high titers of EBV-VCA/IgA, had the poorest prognoses. Therefore, SOX2 or the combination of the SOX2 expression level and EBV-VCA/IgA titers could be valuable to predict distant metastasis or the prognosis of NPC.