The application of ultrasound and microbubble (USmb) has been shown to enhance chemotherapy and radiotherapy (XRT) both in vivo and in vitro. The hypothesis guiding this research is that the combination of ultrasound and microbubbles with chemotherapy (Taxotere – TXT) improves treatment response of radiotherapy of in vitro prostate (PC3) cancer cells. USmb synergistically decreased cell viability when combined with TXT2h+XRT and XRT. Cell viability with the combined treatment (TXT2h+USmb+XRT=2%) decreased by ~28-folds, ~19-folds and ~11-folds compared to XRT alone (57%), TXT2h+XRT (37%) and USmb+XRT (22%), respectively. Cell viability with USmb+XRT (22%) decreased by ~2.5 folds compared to XRT alone. Effectiveness of the combined treatment depended on chemotherapy dose and treatment duration as well as microbubble concentration. The therapeutic application of USmb may enhance cancer cell death by chemotherapy and radiotherapy and reduce their toxic side effects.