Abstract: To explore the efficacy and safety of the bortezomib combined with doxorubicin and dexamethasone ( PAD ) regimen in the treatment of refractory/advanced senile mantle cell lymphoma. Methods: The activity and safety of the PAD regimen were investigated in 5 senile patients with refractory/ advanced mantle cell lymphoma. Four to six 21-day cycles of PAD regimen consisted of bortezomib ( 1.3 mg/m2, days 1, 4, 8, and 11 ), doxorubicin ( 10 mg, day 1 ), dexamethasone ( 40 mg, days 1-4 ). Results: Four/five patients achieved ≥PR response, with 2 patients achieving a complete response (also negative for disease activity by positron emission tomography scanning ). Median progression free and overall survival was 12.3 ( 3.5-23.8 ) and 31.8 ( 6.3-41.7 ) months, respectively. The toxic effects of the PAD regimen included grade II thrombocytopenia (2/5), grade IV thrombocytopenia (1/5), grade II neutropenia ( 2/5 ), grade II fatigue ( 1/5 ), grade II peripheral neuropathy ( 1/5 ), herpes zoster ( 1/5 ). Conclusions: Bortezomib combined with doxorubicin and dexamethasone might be a promising therapy, with efficacy and manageable adverse events in senile patients with refractory/advanced mantle cell lymphoma.