The prevalence of nasopharyngeal cancer (NPC) is high in the southern area of China and some other districts in the world. The pathogenesis of NPC is unclear. It is reported that some microRNAs (miR) are involved in the progression of NPC. This study aims to investigate the role of miR-21 in the induction of immune tolerance of NPC. In this study, NPC tissue was collected from patients with NPC. Assessment of miR was performed with real time quantitative RT-PCR. Western blotting was used to assess proteins of interleukin 10 and nuclear factor I-A (NFI-A). Immune cells were analyzed by flow cytometry. The results showed that NPC cell line C666-1 and surgically removed NPC tissue expressed miR-21, which was upregulated by the presence of the Toll-like receptor 3 ligand, Poly I: C. Exposure to miR-21 increased the expression of NFI-A and interleukin (IL)-10 in naive B cells. High frequency of IL-10(+) B cells was detected in the NPC tissue. The NPC- or miR-21-primed B cells suppressed cytotoxic CD8(+) T cell activities. We conclude that NPC-derived miR-21 induces IL-10(+) B cells; the latter is capable of suppressing CD8(+) T-cell activities. miR-21 may be a potential target in the treatment of NPC.