e16185 Background: Combining sintilimab with IBI305 has shown significant survival benefits over sorafenib in first-line HCC treatment. Our prior study has indicated improved outcomes with sintilimab and bevacizumab biosimilar (IBI305) in combination with HAIC for HCC (Clinical trial: NCT05029973). This study aims to evaluate combining HAIC with sintilimab and IBI305 for initial unresectable HCC in real word. Methods: Eligible patients (pts) had histologically or cytologically diagnosed or clinically confirmed HCC, with China liver cancer staging (CNLC) stage Ib-IIIb, no prior systemic treatment, Child-Pugh A or B, and ECOG 0 or 1. Patients were administered FOLOFOX-HAIC, combined with intravenous Sintilimab (200 mg, Q3W) and intravenous IBI305 (7.5 mg/kg, Q3W). Primary endpoints included objective response rate (ORR) and disease control rate (DCR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included surgical conversion rate, R0 resection rate, and pathological complete response (pCR) rate. Results: Data were collected from 106 patients (from Apr, 2021 to Jul, 2023), median age 61, with the majority being male (91, 85.9%), ECOG 0 (106, 100%), and classified as Child-Pugh A (82, 77.4%). CNLC staging: Ib (19), IIa (2), IIb (20), IIIa (42), IIIb (23). HBV infection: 84 (79.3%), HCV: 3 (2.8%). AFP levels were > 400ng/ml in 53 patients (50.0%), with tumor diameters > 10 cm in 47 patients (44.3%). Single tumors were noted in 35 patients (33.0%), vascular invasion in 60 patients (56.6%), and extrahepatic metastasis in 26 patients (24.5%). Among the 106 patients evaluable for response, ORR was 39.6% with 42 patients demonstrating partial responses (PR); DCR was 96.2% (102/106), comprising 42 PR, 60 stable disease (SD). The surgical conversion rate was 40.56% (43/106), achieving R0 resection in all 43 patients and complete pathological response (pCR) in 9/43(20.9%) patients and major pathological response (MPR) in 12/43 (27.9%). The 1-year progression-free survival (PFS) and overall survival (OS) rates were 54.5% and 74%, respectively. The 2-year PFS and OS rates were 41.4% and 58.6%, respectively. No new safety signals were observed, and no treatment-related adverse events (TRAEs) led to death. Conclusions: Combining HAIC with Sintilimab and IBI305 as conversion therapy for unresectable HCC shows promising benefits with manageable safety.