Background: Downstaging radiotherapy provide patients with initially unresectable or borderline resectable hepatocellular carcinoma (HCC) a chance to receive conversion curative resection. This study intended to prospectively evaluate the efficacy and toxicities of downstaging radiotherapy for HCC with macroscopic vascular invasion. Methods: From March 2018 to May 2020, 30 HCC patients with macroscopic vascular invasion were prospectively treated with transcatheter arterial chemoembolization combined with radiotherapy (n = 24) or radiotherapy alone (n = 6). The primary study endpoint was overall survival (OS). The secondary study endpoints were progression free survival (PFS), downstaging success rate, and surgical conversion rate. Adverse events were assessed. Results: The follow-up time of the entire cohort was 24 months. The median OS of the entire cohort was 22.0 months, 12-, and 24- months OS was 60.0% and 47.8%, respectively. The median PFS was 13.0 months, 12-, and 24-months PFS was 53.3% and 27.0%, respectively. During downstaging window phase within 3-6 months, 22 patients were evaluated as downstaging success by clinical imaging. Among them, 9 patients underwent R0 radical hepatectomy and 13 patients refused surgical treatment, yielding a downstaging success rate of 73.3% (22/30 patients) and a surgical conversion rate of 30.0% (9/30 patients). Of the patients who underwent surgery, 4 patients (44.4%) experienced ≥ grade 4 postoperative complications, including 2 (22.2%) with gastrointestinal bleeding and 2 (22.2%) with bile leakage. Conclusions: For unresectable or borderline resectable HCCs complicated with macroscopic vascular invasion, high-dose radiotherapy-based treatment provided favorable downstaging efficacy, surgical conversion rate, and survival outcomes. Clinical trial information: ChiCTR1800015350.