Background: More than 70% of hepatocellular carcinoma (HCC) patients are in the intermediate or advanced stages at the time of diagnosis. TACE, TKI and PD-1 antibody are all recommended for patients with unresectable HCC (uHCC) according to Chinese HCC guidelines. There are few scientific trials to back up the safety and effecacy of TACE+TKI+PD-1 antibody for the treatment of uHCC and conversion resection. In this study, we explored the safety and efficacy of the TACE+TKI+PD-1 antibody in uHCC. Methods: This is a prospective, multicenter, cohort study (NCT04997850). Key Eligibility Criteria:18 years old ≤ age ≤ 70 years old; HCC confirmed by histopathology or cytology; No systemic treatment history. ECOG PS score 0-1; Child-Pugh A/B; BCLC stage B/C.Experience group: TACE + Lenvatinib (12mg when≥ 60kg/8mg when < 60kg QD) + Camrelizumab/ Sintilimab (200 mg ivgtt Q3W);Control group: TACE. Results: From Sep 2020 to May 2021, 38 patients were enrolled in experimental group (Table). At the cutoff date (Sep 10 2021), the median follow-up was of 33.34 weeks (Table). The conversion resection rate was 50% (19/38), and the conversion success rate was 52.6% (20/38). Among the 19 patients, 5 cases achieved complete pathological response and 1 case achieved major pathological response. The 48 weeks’ OS rate and PFS were 96.4% (95%CI 92.9% to 99.9%) and 91.7%(95%CI 85.8% to 97.4%).22 patients had level 3 treatment related adverse events (TRAE), there were no level 4 and 5 TRAEs. At the last follow-up, the ORR rate based on mRECIST was 84.2%, and the DCR rate was 94.7% (Table). Conclusions: TACE + Lenvatinib + PD-1 antibody is safe and effective, and conversion resection after the triple-treatment is feasible for uHCC. Clinical trial information: 04997850.