Objective To study the effectiveness and toxicity of ifosfamide(IFO) combined with venorelbine(VRL) in patients with nasopharyngeal carcinoma(NPC) refractory to platinum based chemotherapy. Methods The chemotherapy protocol consisted of intravenous infusion of IFO at the dose of 1200 mg/m2 from day 1 to day 5 with uroprotection of Mesna in infusion at 0,3,6 hours following initiation of IFO and VRL at the dose of 25 mg/m2 at day 1 and day 5. The protocol was repeated every 3 weeks. All patients received at least 2 cycles of chemotherapy. Results Among 25 patients enrolled into the study, 2 patients achieved complete remission, 12 patients achieved partial remission with an total remission rate of 56.0 % and 8 patients had stable disease with clinical benefit rate of 88.0 %. 3 patients had disease progression. Median time to progression was 7.1 months(range:2.0～21.0 months) and 1-year survival rate was 55 %. The main toxicities were myelotoxicity and phlebitis. Conclusion The results indicate that IFO combined with VRL in patients with NPC refractory to platinum based chemotherapy has moderate activity ascompany with tolerable toxicities.