Ethanol ablation (EA) is a safe and effective method for treating small liver cancer. However, the ethanol is rapidly washed out by blood perfusion, preventing its accumulation within tumors. Microbubble-enhanced ultrasound (MEUS) is capable of disrupting tumor and liver circulation. We hypothesized that this disruption could be used to enhance EA of normal liver tissue. We treated surgically exposed rabbit liver with a combination of MEUS and EA. The controls were treated with only MEUS or 0.05 mL EA. MEUS treatment was administered with a high-pressure-amplitude, pulsed therapeutic ultrasound device and intra-venous injection of microbubbles. Therapeutic ultrasound was delivered at an acoustic pressure of 4.3 MPa and a duty cycle of 0.22%. Contrast-enhanced ultrasound was performed to estimate liver blood perfusion. Livers were harvested for necrotic volume measurements 48 h after treatment. Contrast-enhanced ultrasound demonstrated that liver perfusion was temporally arrested, with a significant peak intensity decline from -46.9 ± 3.8 to -64.0 ± 3.3 dB, after MEUS treatment. The mean volume ablated in MEUS + EA-treated livers (3.3 ± 2.3 cm(3)) was more than 10 times larger than that in livers treated only with EA (0.3 ± 0.2 cm(3)). The volume of liver ablated by MEUS treatment alone was minor, scattered and immeasurable. These results indicate that MEUS disruption of the liver circulation can greatly promote EA of liver.