Abstract. Castration-resistant prostate cancer (PCa) is difficult to treat. Autophagy, which is an evolutionarily conserved mechanism, plays an important role in cancer development. The balance between cell death and survival in different stages varies in cancer development. The role of autophagy in PCa development has not yet been fully elucidated. Ultrasound may be of value in the treatment of PCa. The aim of the present study was to investigate the association between autophagy and ultrasound combined with microbubbles. The MTT assay was used to evaluate cell viability. Autophagy was observed by transmission electron microscopy. Reverse transcription-polymerase chain reaction and western blot analysis were used to assess the expression of autophagy-related genes. The results revealed that cell viability was significantly reduced by ultrasound combined with microbubbles in DU145 PCa cells. The present study demonstrated that ultrasound combined with microbubbles induced autophagy and autophagy-related DU-145 cell death. Notably, these findings highlighted additional mechanisms that suggest the potential of ultrasound-modulated autophagy as a novel therapeutic strategy for PCa.