Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignant tumor. Recently, cidofovir, an anti-viral drug which is an acyclic nucleoside analogue, has been reported to have an anti-tumor potential. Two patients with NPC, who had previously received multi-round therapy, were treated with cidofovir. Cidofovir was topically injected in and around the tumor once every 3 weeks (originally 75 mg/ml sulution, diluted to 15 mg/ml just before injection, 37.5 mg of cidofovir at a time). Tumor growth was suppressed for several months around the injection site in each patient. EBV-encoded RNAs in situ hybridization revealed the reduction of the tumor cell population; however, the EBER expression was still maintained in the NPC tumor cells. Although the anti-tumor mechanism remains unclear, these results suggest that cidofovir is actually an effective and safe agent for the treatment of NPC.