Background: Drug nano-carriers are one of the most important tools for targeted cancer therapy so that undesired side effects of chemotherapy drugs are minimized. In this area, the use of ultrasound can be helpful in controlling drug release from nanoparticles to achieve higher treatment efficiency.Objective: Here, we studies the effects of ultrasound irradiation on the release profile of 5-fluorouracil (5-Fu) loaded magnetic poly lactic co-glycolic acid (PLGA) nanocapsules.Methods:  5-Fu loaded magnetic PLGA nanocapsules were synthesized by multiple emulsification method. Particle size was measured by dynamic light scattering (DLS) and transmission electron microscope (TEM). The pattern of drug release was assessed with and without 3 MHz ultrasound waves at intensities of 0.3, 0.5 and 1 w/cm2 for exposure time of 5 and 10 min in phosphate-buffered saline (PBS).Results: The size of nanoparticles was about 70 nm. Electron microscope images revealed the spherical shape of nanoparticles. The results demonstrated that the intensity and exposure time of ultrasound irradiation have significant effects on the profile of drug release from nanoparticles.Conclusion:  It may be concluded that the application of ultrasound to control the release profile of drug loaded nanocapsules would be a promising method to develop a controlled drug delivery strategy in cancer therapy.