Limited data have been reported regarding the use of arsenic trioxide (ATO) in the treatment of patients with relapsed or refractory malignant lymphoma; therefore, the present phase II study evaluated the efficacy and toxicity of ATO in such patients. A total of 35 patients were treated with ATO (0.25 mg/kg) infused for 1 h daily, 5 days a week, for a 6-week cycle. Patients were evaluated for the efficacy and toxicity of this regimen. The primary outcome evaluated was the overall response rate (ORR), including the complete and partial response rates. The secondary outcomes evaluated were the overall survival (OS), progression-free survival (PFS), and toxicity. Tumor response data were obtained from all 35 enrolled patients. The ORR was 43%, including complete responses in four patients (11%) and partial responses in 11 patients (31%). The median duration of response was 16 weeks (range 11-23 weeks). The median OS was 79 weeks (range 14-171 weeks), and the median PFS was 55 weeks (range 14-135 weeks). Grade I or II hematological toxicities were the most commonly reported adverse events. The results of this study appear promising for the treatment of relapsed or refractory malignant lymphoma, with well-tolerated ATO toxicity.