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The aim of this study was to investigate the therapeutic effects of photothermal targeting of hollow gold nanospheres on lymphoma. Hollow gold nanospheres were modified by PEG (polyethylene glycol) and conjugated to anti-CD138 antibody. The conjugates were then injected into the A20 mouse lymphoma model followed by near-infrared laser radiation (NIR). By examining the level of immunoglobulin G2a secreted by A20 cells and measuring the weight of specimen biopsy, tumorgenesis was determined. Finally, the possibility of lymphoma-targeted photothermal therapy was evaluated. Anti-CD138 antibody-conjugated hollow gold nanospheres (HAuNs-CD138) were prepared and the A20 mouse lymphoma model was established. After NIR treatment, A20 lymphoma growth was significantly suppressed. HAuNs-CD138 treatment represents a potential therapeutic strategy for CD138+ lymphoma.