In order to analyse the mechanism of acoustic and flow coupled fields in the low frequency sonophoresis (LFS) process, an acoustic-piezoelectric-fluid model was built based on the piezoelectric equation, acoustic equation, and turbulence k-ε model, by using the finite element software COMSOL. The amplitudes and distributions of acoustic and flow fields in LFS were calculated, and the drug permeation of an in vitro transdermal experiment was measured after 90 minutes of ultrasonic radiation. The simulated and experimental results showed that there was a large amount of cavitation and folding on the skin of LFS, which suggested that the acoustic cavitation effect and alternating load occur on the epidermis, and that the folds may have been caused by water flow or vortex flow field. Further, the flow began on the sound radiation surface in an ultrasonic transducer and circulated to the transducer’s horn profile, contributing to the stirring effect; the largest value of flow velocity happened under the radiation face and reached 0.55 m/s when the input electrical power was 5.5 W, accompanied with eddy currents above the skin; and acoustic field helps promote permeability in LFS, and the flow field can mix drug solution and expand permeation channels role to support the promotion.