Background <p>The global incidence of hepatocellular carcinoma (HCC) is steadily rising, and the disease is associated with poor survival outcomes. As a multicentric cancer with a high recurrence rate, surgical resection alone is often not sufficient for a curative treatment. This study aimed to identify factors that predict its efficacy in patients with HCC classified as borderline resectable according to the BR-HCC Expert Consensus 2023.</p> Methods <p>This study retrospectively analyzed 30 patients with borderline resectable HCC who were treated with Lenvatinib as their initial therapy. The study retrospectively examined the predictive factors for the disease control rate (DCR) following Lenvatinib treatment. A secondary objective was to evaluate the impact of the treatment on overall survival and identify cases that showed a significant response.</p> Results <p>The presence of a single tumor was found to be the only independent predictive factor for treatment response. The 5-year survival rate for patients in the stable disease (SD) and partial response (PR) groups was 33.3%, which was significantly higher than that of the progressive disease (PD) group. Of the six patients who achieved a PR with Lenvatinib, four had a single tumor with vascular or biliary invasion or extrahepatic metastasis. Similarly, the two patients who underwent radical resection after Lenvatinib treatment also had a single tumor with these characteristics.</p> Conclusions <p>The presence of a single tumor may be a crucial factor in the use of Lenvatinib for borderline HCC.</p>