496 Background: Hepatocellular carcinoma (HCC) disproportionately affects minorities, particularly Black and Hispanic patients, and patients of lower socioeconomic status. These patients are more likely to be diagnosed with advanced disease, less likely to receive curative therapies, and have higher mortality rates. Data on the impact of disparities on patterns of systemic treatment (STx) in these disadvantaged groups are limited. This retrospective observational study used a large real-world database to explore differences in patient characteristics and patterns of STx based on race/ethnicity (R/E) and insurance status. Methods: 1283 patients diagnosed with HCC from 2011 to 2021 with known race, insurance, documented metastatic disease (mHCC), and without prior transplant from the nationwide de-identified Flatiron Health EHR-derived database were selected and analyzed. Chi-squared tests, T-tests, and log-rank tests were used to assess how R/E and insurance (Medicaid vs non-Medicaid) were related to HCC risk factors, number of lines of systemic therapy (LOT), and time from metastatic diagnosis (mDx) to start of STx. Results: Of 1283 patients evaluated, there were 750 white (W), 175 Black (B), 122 Hispanic (H), 69 Asian (A), and 167 patients with other race. B and H patients had the highest rates of known HCV (B 74.3%, H 48.4%, W 41.2%, A 23.2%; p < 0.001) and A patients were most likely to have known HBV (53.6%). More B and H patients had Medicaid (W 10.9%, A 14.3%, B 18.9%, H 28.5%, p < 0.001) and had the lowest rates of Medicare with commercial insurance (W 25.9%, A 21.7%, B 12.6%, H 14.6%, p < 0.001). H patients had the lowest rates of commercial insurance (H 39.3%, W 41.3%, A 44.9%, B 44.6%, p < 0.001). There was no significant difference in likelihood of receiving approved STx after mDx based on R/E. A patients had the highest rates of receiving multiple LOT (A 37.5%, W 18.5%, B 18.9%, H 20.5%; p = 0.285). 30-40% of patients with mHCC did not receive any STx and only 18-27% received more than 1 LOT. Most patients received STx for mHCC within 2 months without a significant difference based on R/E. There was no difference in unadjusted time to treatment based on insurance. Conclusions: This large-scale analysis did not reveal significant differences in the likelihood of receiving STx after mDx based on R/E or insurance. This analysis has limited data from safety net hospitals, which may impact our ability to fully elucidate disparities in the medical management of advanced HCC. 30-40% of patients with mHCC did not receive any STx and only 18-27% received more than 1 LOT, indicating that a significant portion of patients with HCC may be undertreated even in academic and community practice settings. Large scale real-world database analysis is a critical way to better understand treatment and survival outcomes in this population, which is expected to have the highest rates of HCC over the next 10 years and has been underrepresented in HCC trials.