e16602 Background: Outcomes remain poor for patients with advanced hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC), antiangiogenic agents, and immune checkpoint inhibitors (ICIs) are available monotherapy options. Considering different anti-malignancy mechanisms, combining these three modalities may improve outcomes. We aimed to assess the efficacy and safety in a small cohort treated with HAIC combined with Apatinib and ICI (Toripalimab) for advanced HCC patients. Methods: We performed a retrospective study included patients with advanced HCC treated in the Sun Yat-sen University Cancer Center. Patients received 6 treatment cycles of 21 days, with HAIC given over an initial period of 50 hours (oxaliplatin 85 mg/m2, then folinic acid 400 mg/m2, then fluorouracil 2500 mg/m2). Patients also received apatinib (250 mg daily, starting day 8 of cycle 1), toripalimab (240 mg on day 4 of each cycle, starting with cycle 2), both continuing after the HAIC cycles until disease progression. Disease control was assessed using the RECIST 1.1 and mRECIST criteria. Safety was assessed using the CTCAE 5.0. Blood biomarkers (AFP and PIVKA-II) were log transferred and compared at baseline and last follow-up. Results: From April to August 2019, 6 patients (5 males, 51.7±11.6 years) were included. All patients finished 6 cycles of HAIC. After a median follow-up of 7.0 (range, 3.9-8.3) months, all patients remained objective response (6 PR by RECIST; 3 CR and 3 PR by mRECIST). Median time to response was 1.3 (range, 0.7-2.0) months. Blood logAFP (baseline: 3.2±1.6, last follow-up: 1.3±1.4; p = 0.029) and logPIVKA-II (baseline: 4.4±0.6, last follow-up: 2.0±1.4; p = 0.006) levels were significantly decreased after treatment. The most common adverse events (AEs) included hypertension, palmar-plantar erythrodysesthesia syndrome, and anorexia, observed in all patients. Four patients had Grade 3 AEs (myelosuppression in 2; palmar-plantar erythrodysesthesia, hypothyroidism, anorexia, hyperbilirubinemia and hypokalemia in 1). No Grade 4/5 AEs occurred. Conclusions: In patients with advanced HCC, treatment with strategically timed triple combination therapy of HAIC, apatinib, and toripalimab shows promising clinical benefit and safety. [Table: see text]