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e16113 Background: Management of advanced hepatocellular carcinoma (HCC) remains a challenge. IMbrave150, a pivotal trial reported impressive overall survival benefit using combination strategy of atezolizumab and bevacizumab compared to sorafenib. We wonder the efficacy and safety when combining radiotherapy with immune checkpoint inhibitors (ICIs), which radiation might provide better local treatment and possible trigger abscopal effect. The aim of this study is retrospectively reporting the real-world efficacy and tolerability of proton beam or photon radiation plus ICIs in patients with advance stage HCC. Methods: We retrospectively reviewed all BCLC stage C HCC patients who have received combination therapy with ICIs plus proton or photon therapy with well documented basic characteristics and prompt treatment efficacy evaluation between 1st of January 2016 to 31st of October 2019 at a single medical center in Taiwan. 20 patients had ICIs plus proton and 32 patients had ICIs plus photon were included for analysis. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier estimator. Results: Baseline characteristics were generally similar between ICIs plus proton or ICIs plus photon, while most patients in proton group did not receive prior systemic treatment and had less local therapies prior ICIs combine with radiotherapy. Median follow-up time was 10.7 months. The median Progression free survival (PFS) was not reached in ICIs plus proton group and 3.6 months (95% CI 2.7-4.6) in ICIs plus photon group (P = 0.007). The median OS was not reach in ICIs plus proton group and 12.1months (95% CI 6.4-17.7) in ICIs plus photon group (P = 0.007). Comparing ICIs plus proton group versus photon group, objective tumor response is 50% versus 9%, disease control rate is 80% versus 47% in each group. During follow-up, 7 patients (35%) in proton group achieved complete remission (CR). There was difference in radiation filed, 19 patients (95%) in proton group and 15 patients (47%) in photon group targeted on liver tumors, and more patient received > 50Gy treatment dose in proton group compared to photon group (90% versus 20%). Proton group has lower failure rate in both inner- or out-field compared to photon group. Grade 1 to grade 2 skin-dermatological and gastrointestinal toxicity remained the most frequent reported adverse events in both groups. There are only one therapy related grade 3 dermatitis in ICIs plus proton group and one grade 3 hepatitis, one grade 5 pneumonitis in ICIs plus photon group. Conclusions: This study reported real-world efficacy and safety of ICIs in combination with proton or photon therapy. Most adverse events were manageable. The combination of ICIs and proton therapy has impressive CR rate and OS benefit. Further prospective randomized trial is warranted for confirm our finding.