Doxorubicin (DOX) is one of the most important medicines used for the treatment for B cell lymphoma, yet its clinical efficacy is often limited by severe adverse effects. Drug-loaded microbubbles, combined with ultrasound (US) irradiation, has shown great promise in reducing DOX-induced side effects and improving therapeutic efficacy. Nevertheless, these drug-loaded microbubbles are non-targeted microbubbles with comparatively suboptimal efficiency. Therefore, we synthesized targeted and DOX-loaded microbubbles (DMs), combined with US irradiation, for triggering drug release in lymphoma B cells. DMs were coated with rituximab via a biotin-avidin linkage to target Raji cells that overexpress the CD-20 antigen. In the present study, the cell viability after treatment with rituximab-conjugated DMs (RDMs) containing 0.25, 0.5 and 1.0 µg/ml DOX + US was 45.69±6.85, 25.31±2.60 and 15.67±2.83%, respectively, which demonstrated that RDMs + US produced significantly higher cytotoxicity than the other treatments. The early apoptosis ratio in the Raji cells at 48 h after the treatment was 32.4±2.84%, which was notably higher than the ratio in the other treatment groups. The results confirm the hypothesis that US-mediated targeting of CD-20-positive B cell lymphoma and the use of DMs may improve the DOX therapeutic efficiency.