In the US, incidence rates of hepatocellular carcinoma (HCC) have more than tripled and death rates have doubled since 1980. In 2022, it is expected for 41,260 new cases to be diagnosed with 30,520 deaths. Many etiologies contribute to the development of HCC including alcoholic cirrhosis, cryptogenic cirrhosis, HCV, HBV, NASH, and genetic disorders like hereditary hemochromatosis. An increasing number of patients are not candidates for curative options such as resection or transplant and the role of alternative liver directed as therapies has increased. SBRT has emerged as a safe and effective option, but there is little known about the outcomes related to the etiology of the HCC. The purpose of this study is to characterize the rates of toxicity and efficacy between different HCC etiologies in patients who were treated with SBRT. A single institutional database was compiled of all patients with HCC who were treated with SBRT. Patients with HCC etiologies of HCV, alcoholic cirrhosis, or NASH cirrhosis who received SBRT and monitored with liver function tests and imaging (MRI or CT) and were not transplanted were included Demographic information, disease etiology, all treatment courses, lab values, radiologic response, and follow-up were collected on all patients. SPSS was used to analyze the data. Consecutive patients (n = 37, 43 courses of radiation) who received SBRT between 2013- January 2022 were included. Most patients were male (n = 32, 86.5%) and average age was 64.73 ± 7.42 years (range: 50-82 years). A majority of patients had either HCV or HCV and alcoholic cirrhosis (n = 28, 75.7%) and there were no baseline difference in child Pugh score, tumor size, or number of prior treatments. Most patients were treated with 50Gy/5 fx (n = 26, 70.3%) with 5 others being treated with 45Gy/5fx to meet mean liver constraints. Most patients had a decrease in ALT (n = 22, 59.5%) while almost half of patients had a decrease in AFP (n = 14, 48.3%) at average follow-up of 11.84 ± 5.35 months. There was a significant correlation between HCC etiology and change in bilirubin with patients with HCV being more likely to have increases in total bilirubin (χ2 (6) = 17.5, p < 0.01). Patients with HCV induced cirrhosis may be more fragile and have a significant increased risk of toxicity after SBRT based on total bilirubin changes. Most patients did have a decrease in ALT showing potential for some improvement in liver function with SBRT. However, almost half of patients have some biologic efficacy with SBRT independent of HCC etiology. Further studies should include looking at the biologic differences in the etiologies and what treatment liver-directed therapies may be best for each population.