4082 Background: Although there is no standard perioperative treatment for resectable HCC characterized with high recurrence rate, the strategy of immunotherapy combined with targeted agents is promising in neoadjuvant/adjuvant therapy in various tumors. Methods: In this perspective, single-arm, exploratory phase II trial (NCT04297202), eligible patients (pts) were systemic treatment-naive resectable HCC in intermediate/advanced stage. Preoperative combined treatment of anti-PD-1 antibody camrelizumab (200 mg q2w for 3 cycles) and VEGFR-2 inhibitor apatinib (250 mg qd for 21 days) was started on day 1 cycle 1. On the 7th day after the 3 cycles, radiological imaging was assessed to confirm whether to conduct the hepatectomy. Four weeks after the surgery, combined treatment (camrelizumab 200 mg q3w, apatinib 250 mg qd, 3 weeks per cycle) was resumed for the postoperative 8 cycles. The primary endpoint was major pathologic response (MPR) defined as 50%-99% tumor necrosis in resected tissue. Gene expression profiles (GEPs) using immune-related RNA with pre-treatment specimens were analyzed. The association between immune signatures and pathological response (responders (R) vs. non-responders (NR)) was assessed. Results: A total of 20 pts were enrolled between Dec 5, 2019 and Jan 27, 2021, with a median follow-up of 5.7 months (range 0.7-9.0). All pts were ECOG PS 0-1 and Child-Pugh class A. There were 85% pts with hepatitis B and 10% with hepatitis C, and 55% in BCLC stage B, 35% in stage C and 10% in stage A. In preoperative phase, with 2 withdraw of informed consent form, partial response was reached in 3/18 (16.7%) and 8/18 (44.4%) pts per RECIST 1.1 and mRECIST, respectively, while disease progression was found in 1/18 (5.6%) pts impossible for hepatectomy, which made the resection rate 17/18 (94.4%). After the surgery, one was found to be combined hepatocellular-cholangiocarcinoma by histopathological examination and failed to proceed the postoperative study. The rates of MPR and pathological complete response (pCR) were 5/17 (29.4%) and 1/17 (5.9%), respectively. The preliminary analysis of GEPs (R:NR = 3:4) revealed higher levels of chemokines ( CXCL10 and CXCL11) in responders and higher MS4A4A (marker gene of macrophages ) in non-responders. The most common TEAEs included hypertension (95%), proteinuria (40%), AST elevation (40%), and platelet count decrease (45%). Grade 3 TEAEs were hypertension (20%), rash (10%), and platelet count decrease (10%). No grade 4/5 TEAEs was observed. The most common surgical complications were ALT and AST increase each with the incidence of 70% (all grades) and 45% (grade ≥ 3). Conclusions: This study preliminarily demonstrated that the perioperative treatment of camrelizumab combined with apatinib improved the MPR and pCR with managable safety in intermediate/advanced resectable HCC. Clinical trial information: NCT04297202.