Brain tumors have a poor prognosis. Early, accurate diagnosis and treatment are crucial. Although brain surgical biopsy can provide an accurate diagnosis, it is highly invasive and risky and is not suitable for follow-up examination. Blood-based liquid biopsies have a low detection rate of tumor biomarkers and limited evaluation ability due to the existence of the blood-brain barrier (BBB). The BBB is composed of brain capillary endothelial cells through tight junctions, which prevents the release of brain tumor markers to the human peripheral circulation, making it more difficult to diagnose, predict prognosis, and evaluate therapeutic response through brain tumor markers than other tumors. Focused ultrasound (FUS)-enabled liquid biopsy (sonobiopsy) is an emerging technique using FUS to promote the release of tumor markers into the circulatory system and cerebrospinal fluid, thus facilitating tumor detection. The feasibility and safety data from both animal models and clinical trials support sonobiopsy as a great potential in the diagnosis of brain diseases.