Objectives To evaluate the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of hepatocellular carcinoma (HCC) unsuitable for standard loco-regional therapies. Materials and methods Patients with 1–3 inoperable HCC lesions with diameter ≤6 cm were treated by SBRT. According to lesions size and liver function, two prescription regimens were adopted: 48–75 Gy in three fractions or 36–60 Gy in six fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points of this study were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and progression-free survival (PFS). Results Forty-three patients with 63 HCC lesions were irradiated. All patients had Child–Turcotte–Pugh class A or B disease. Thirty lesions (48 %) were treated with 48–75 Gy in three consecutive fractions, and 33 (52 %) received 36–60 Gy in six fractions. Median follow-up was 8 months (range 3–43 months). Actuarial LC at 6, 12 and 24 months was 94.2 ± 3.3, 85.8 ± 5.5 and 64.4 ± 11.5 %, respectively. A biological equivalent dose (BED) >100 Gy and GTV size were significant prognostic factors for LC in univariate analysis ( p  < 0.001 and p  < 0.02). Median OS was 18.0 ± 5.8 months. Actuarial OS at 6, 12 and 24 months was 91.1 ± 4.9, 77.9 ± 8.2 and 45.3 ± 14.0 %, respectively. Univariate analysis showed that OS is correlated with LC ( p  < 0.04), BED >100 ( p  < 0.05) and cumulative gross tumor volume GTV <5 cm ( p  < 0.04). Median PFS was 8 months, with a 1-year PFS rate of 41 %. A significant (≥grade 3) toxicity was observed in seven patients (16 %) 2–6 months after the completion of the treatment. No classic radiation-induced liver disease was observed. Conclusion Stereotactic body radiation therapy is a safe and effective therapeutic option for HCC lesions unsuitable to standard loco-regional therapies, with acceptable local control rates and low treatment-related toxicity. The significant correlation between LC and higher doses and between LC and OS supports the clinical value of SBRT in these patients.