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Histotripsy is a novel ultrasound-guided ablation technique that has been approved by the US Food and Drug Administration as a medical device for the noninvasive destruction of liver tumors. The noninvasive, nonthermal, nonionizing mechanical mechanism by which it destroys tumor tissues makes it an appealing local therapy option in the treatment of patients with early-stage hepatocellular carcinoma (HCC). In this article, the authors review the current evidence base for histotripsy in HCC and explore its potential role in routine care based on technical, safety, and clinical considerations. They then describe the evidence gaps that remain with respect to histotripsy's treatment efficacy, comparative effectiveness, and safety relative to established local therapy options including thermal ablation, transarterial chemoembolization and radioembolization, and stereotactic body radiotherapy. Although the current body of evidence supports the technical feasibility, short-term safety, and early local tumor control of histotripsy in the treatment of patients with HCC, standardized response assessments, rigorous prospective evaluations of durable oncologic outcomes, and direct comparisons with existing therapies in well-defined patient populations are still needed before histotripsy can be fully integrated into standard HCC care.