Tomotherapy-based SBRT is often utilized for treating brain or spine lesions; however, its role in treating intrahepatic tumors has not been explored. A phase 1 dose-escalation trial was conducted to determine the feasibility and toxicity of Tomotherapy-based SBRT for primary HCC. Eligible patients had Child-Turcotte-Pugh’s Class (CTP) A or B, were not candidates for resection, had 1-3 lesions and cumulative tumor diameter less than or equal to 6 cm. Abdominal compression and 4-dimensional computed tomography was used during SBRT simulation. Dose-escalation began at 36 Gy in 4 fractions (9 Gy/fraction) with a subsequent planned escalation of 2 Gy/fraction per dose level. All patients were treated every-other-day with on-board mega-voltage CT for image-guidance. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events v3.0 grade 3 or greater gastrointestinal toxicity. Modified Response Criteria in Solid Tumors (mRECIST) was used to evaluate treatment response and survival was measured from the last day of SBRT. Eighteen patients with 22 lesions were enrolled. The median cumulative tumor diameter was 2.1 cm (range, 1.0-4.4 cm). Dose was initially escalated to 52 Gy (13 Gy/fraction) without DLT. The protocol was amended for a further escalation to 60 Gy (15 Gy/fraction). Radiologic complete response (CR) was achieved in 16 patients (88.9%) with median time to CR of 6.0 months (range, 0.7-12.3 months). Changes in alpha fetoprotein (AFP) level were well correlated with radiologic response among patients with initial AFP elevation. Nine patients experienced disease progression: 2 local, 5 outfield intrahepatic, and 2 distant failures. No local failure occurred at dose levels 3 and 4. Dose-limiting toxicity was not reached. Grade 3 hematologic toxicity was reported in five patients: all of these patients had grade 1 or 2 hematologic events prior to SBRT. No GI toxicity greater than grade 1 occurred. With median follow-up of 20 months (range, 8-33 months), 1 and 2-year local control rates were 76.9% and 70.5%, progression-free survival (PFS) were 54.3% and 47.5%, and overall survival were 100% and 70.0%. Multi-segmental recurrences prior to SBRT was associated with poor PFS in univariate (P = .038) and multivariate analyses (P = .056). Tomotherapy-based SBRT was well tolerated with encouraging preliminary results. A confirmatory phase 2 trial is currently underway.