Many patients with NHL suffer from refractory or relapsed disease, and platinum-based combination therapy is widely used for salvage therapy. Oxaliplatin, a novel platinum derivative, is a more potent cytotoxic agent than cisplatin, demonstrating greater efficacy against many tumor cell lines, including lymphoma cell lines. Clinical studies of oxaliplatin for other malignancies have shown a favorable toxicity profile. The objective of this phase II trial was to investigate the activity of oxaliplatin in patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL). Patients with measurable NHL who had experienced failure of one or more prior chemotherapy regimens were considered eligible. They were required to have an ECOG performance status £ 2 and adequate organ function. Patients were excluded if they had HIV infection, CNS lymphoma, or had chemotherapy or radiotherapy within 4 weeks prior to entering the study. All patients gave their written informed consent to participate. Oxaliplatin was administered at 130 mg/m2 every 21 days for up to six cycles in the absence of progression. Thirty-one patients (23 with aggressive NHL, 8 with indolent NHL) were enrolled on this trial. Thirty eligible patients received oxaliplatin, who were all assessable for toxicity. Response and survival were also analyzed in all 30 patients based on intention to treat analysis. The median patient age was 62 years, and most of the patients had an ECOG performance status of 0 or 1. The most common toxic effect was sensory neuropathy (87%). Grade 3 and 4 toxic effects included sensory neuropathy (10%), neutropenia (17%), and thrombocytopenia (20%). Objective responses occurred in 8 (27%) of the patients: 7 with aggressive NHL, 1 with indolent NHL. The median failure-free survival duration in the entire group, aggressive NHL group and indolent NHL group was 3.0, 2.1 and 4.0 months, respectively. It is noteworthy that three of the five patients with MCL (60%) had a significant response to oxaliplatin, including two CRus, with a median FFS duration of 5 months. When patient group is divided by IPI score (0/1 and 2 /3), the median FFS duration was 3.4 months and 2.6 months, respectively. Median response duration for entire group was 3.0 months. In summary, oxaliplatin has modest activity in patients with previously treated NHL, especially those with aggressive disease. The favorable toxicity profile of oxaliplatin warrants further investigation of it either in combination chemotherapy or with targeted biologic therapy.