RATIONALE:: Refractory nasopharyngeal carcinoma is challenging to treat and at present there is no standard treatment or any good choice. PATIENT CONCERNS:: Although the three patients in our case reports had already underwent multiple treatments before, they still suffered from disease recurrence of nasopharyngeal carcinoma. DIAGNOSIS:: They were diagnosed as refractory nasopharyngeal carcinoma. INTERVENTIONS:: A continuous infusion of Endostar, an antiangiogenic agent, combined with chemotherapy and radiation therapy was given to treat the patients. OUTCOMES:: Patients showed complete or partial response to the combined therapy as evidenced by regression of tumors and decrease in plasma Epstein–Barr virus (EBV) DNA load. LESSONS:: Continuous infusions of Endostar in combination with chemotherapy and/or radiation therapy showed promising efficacy and safety. The combination therapy indicates a new approach to treat refractory nasopharyngeal carcinoma.