Here, we describe the anti-tumor mechanism of IMM0306, a fusion protein of CD20 monoclonal antibody (mAb) with the CD47 binding domain of SIRPα, by activating both macrophages and NK cells via blockade of CD47-SIRPα interaction and FcɣR engagement by simultaneously binding to CD47 and CD20 of B cells in different mouse xenograft tumor models. The gene discussed is CD47; the disease is neoplasm.