Background: Immune checkpoint inhibitor (ICI) based therapy has emerged as a therapeutic option in hepatocellular carcinoma (HCC). Approvals were based on clinical trials with strict eligibility criteria limiting generalizability to clinical practice. Further, there is no established post ICI treatment standard. Methods: Patients (pts) with advanced HCC treated with ICI as single agent (ICI-SA) or in combination (ICI-C) across lines of therapy were included in this retrospective study. Results: The cohort consisted of 118 pts: median age 63 years (24, 88); 84% male; 35% Hispanic/Latino, 26% Asian, 19% Non-Hispanic White, 5% Black and 15% unknown. Etiology of cirrhosis: 13% Hepatitis B, 45% Hepatitis C, 16 % alcohol liver disease, 10% NAFLD and 16 % mixed/other; 73% had baseline Child Pugh (CP) A, 25% had CP-B, and 2% had CP-C; ALBI Scores were ≤ -2.60 in 32%, 2.60 < and ≤-1.39 in 48%, and ≥-1.39 in 19% pts; 62% had extrahepatic disease and/or portal invasion; AFP was ≥ 400 ng/mL in 25% of pts. 81% of pts had prior local therapy. First line systemic therapies were: TKIs in 52 pts (44%), ICI-SA in 42 (36%), ICI-C in 15 (13%), clinical trial agent (CTA) in 8 (7%) and chemotherapy in 1 (1%), with a median duration (dur) of 4 months (95% CI 2.3 to 4). Ninety one (77%) and 61 pts (52%) received ≥ 2 or 3 lines of therapy, respectively. Fifty seven pts had ICI-SA and 14 ICI-C in second line or beyond. Median dur of ICI therapy was 4 months (95% CI 3-5) for all lines. Post-ICI therapies included 11% ICI, 30% CTA and 59% TKIs. TKIs included sorafenib (46%), cabozantinib (27%), lenvatinib (15%), and regorafenib (27%). For the 118 pt cohort, mOS was 14 months (95% CI 12-19). For pts treated with ICI in first line, mOS was 11 months (0, 74); post-ICI mOS was 6 months (95% CI 3-9) and mPFS was 3 months (95% CI 2-3). Thirty one pts received a TKI post ICI; mOS for this subset was 19 months (15, 22); mOS from start of TKI post ICI was 6.5 months (4, 12). On multivariable regression analysis, ALBI score was associated with OS (HR 1.63, p=0.02, CI: 1.08-2.27). Conclusions: Pts with advanced HCC and CP-A or B cirrhosis are able to receive sequential systemic therapy including ICI. Survival outcomes in this cohort are impacted by the inclusion of patients with more compromised liver function and less restrictive pt selection compared to clinical trials. Usage of TKIs post ICI is feasible with suggestion of clinical activity but this is an area in need of prospective studies.