Abstract: OBJECTIVE To evaluate promote efficacy of low frequency sonophoresis at 20 kHz on transdermal permeation of lidocaine hydrochloride gel. METHODS The lidocaine hydrochloride gel was preparated, permeation studies were carried out in vitro on excised suckling pig skin over a period of 2 h using one- chamber diffusion cells. The concentration of lidocaine in receptor solution was analyzed by HPLC. The permeation capability of lidocaine hydrochloride gel with and without ultrasound were determined, and compound lidocaine cream was used as a control. Parameters like ultrasound output powers and application time were tested. RESULTS Application of ultrasound could significantly promote the percutaneous permeation of lidocaine hydrochloride. With increasing ultrasonic intensity and duration, the promote effect was significantly enhanced. When ultrasound output power was 2.26 W·cm^-2 and application duration was 5 min, the cumulative amount of permeated lidocaine hydrochloride was 9.3 times higher than passive control, and 2.4 times higher than compound lidocaine cream. CONCLUSION Low frequency sonophoresis can be effectively used to enhance transdermal delivery of lidocaine hydrochloride. Sonophoresis mediated topical delivery of lidocaine hydrochloride can be developed as a drug delivery method for the prevention of pain from needle prick during the injection.