Nasal, nasal-type T-cell/natural killer cell (T/NK-cell) lymphoma is a rare disease, and its prognosis is poor. Between March 1992 and March 2002 we investigated a new L-asparaginase-based salvage regimen to treat the disease and improve response to treatment and 5-year overall survival rate. Eighteen patients with refractory midline nasal, nasal-type T/NK-cell lymphoma, who were resistant to a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-like regimen, received an L-asparaginase-based salvage regimen (L-asparaginase, vincristine, and dexamethasone). Primary involved field radiation was given to the patients after chemotherapy. Ten (55.6%) of the patients achieved complete response (CR). Five patients (27.8%) achieved partial response (PR). The overall response rate (CR + PR) was 83.3%. The 5-year overall survival rate was 55.6%. Results of the preliminary clinical study indicated that the L-asparaginase-based salvage regimen significantly improved the response rate and 5-year survival rate. The findings suggested that the therapy is a promising new salvage regimen for treating refractory midline nasal, nasal-type T/NK-cell lymphoma.