Methotrexate (MTX) is a highly renal and liver toxicity drug used in hematological malignancy treatment in children and adults. High-dose methotrexate (HD-MTX) therapy may cause impairment of kidney and decrease the elimination of MTX, at the same time, the serum concentration of MTX increased. Today the treatment for preventing MTX toxicity after renal shutdown is Carboxypeptidase. We report a patient who experienced nephrotoxicity after the HD-MTX infusions during the treatment for non-Hodgkin lymphoma (NHL) and received hemodiafiltration (HDF) with large dose of leucovorin (LV) to treat MTX intoxication. LV is very potent in the prevention of neurotoxicity and administration of LV could protect the normal cells, but the dosage and duration of LV should be according to the MTX concentration. Although a large dose of LV was applied, the patient's condition did not improve. It was found that the HDF with large dose of LV to save the patient and steadily improved the patient's clinical condition.