Background: Combining a PD-1 inhibitor with tyrosine kinase inhibitor has achieved a high response rate for advanced HCC (aHCC) in first-line settings. Sorafenib remains the approved first-line choice for aHCC and demonstrates survival benefit, manageable toxicity and high accessibility in china. This study aimed to explore the efficacy and safety of sintilimab (anti-PD-1 antibody) combined sorafenib in patients (pts) with aHCC. Methods: This is a single-arm phase II study (CTR2000031242). Eligible pts with aHCC, BCLC stage C or B (unresectable or not applicable for TACE), Child-Pugh scores≤7 and ECOG PS ≤ 1 received first-line treatment of sintilimab (200mg, iv, D1) every 3 weeks plus sorafenib (400mg, po, BID) until disease progression or unacceptable toxicity. Primary endpoints was objective response rate (ORR, per RECIST 1.1), and secondary endpoints included safety, disease control rate (DCR), progression free survival (PFS), duration of response (DOR) and overall survival (OS). Results: As of January 30, 2022, 12 pts were enrolled (males 11; median age 54.5 yrs [range 46-68]; BCLC A/B/C: 1/6/5; Child-Pugh A/B7: 5/7; HBV infection 11). All pts received at least 1 cycles of treatments with median cycles 3.5 [range 1-17]. Median follow-up was 3 months [range 0.7-15]. 12 pts were evaluable for response, with an ORR of 17 % (95%CI, 0.1%-41.4%) and a DCR of 33 % (95%CI, 2%- 64%). The median PFS was 3.2 months and median OS was not reached. All pts were evaluable for toxicity, and 6 (50.0 %) pts had at least one treatment-related AE (TRAE). TRAEs occurring in≥20% of pts were pruritus (25%). 1 pt had grade 3 TRAEs. Conclusions: The combination of sintilimab and sorafenib showed promising clinical activities with manageable toxicity for first-line treatment of aHCC. Clinical trial information: CTR2000031242.