Background: Conversion therapy for unresectable hepatocellular carcinoma (uHCC) has attracted increasing interest in recent years. In 2020 ASCO annual meeting, one abstract reported that the combination therapy of tyrosine kinase inhibitor and anti-PD-1 antibody could be a promising conversion therapy for patients with initially uHCC. This study aims to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and camrelizumab (TACE+LEN+CAM) as a conversion therapy for uHCC. Methods: This single-arm, prospective, multicenter study was conducted on patients diagnosed with HCC (with an Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1 and Child-Pugh class A) who were ineligible for surgery. Enrolled patients received camrelizumab (200 mg every 3 weeks) and lenvatinib (bodyweight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) after TACE treatment. Surgery was performed after treatment response was assessed to meet the criteria of resection. Patients who did not meet the criteria for surgery continued to receive triple treatment until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR)and safety. Secondary endpoints included percentage of patients amendable to surgery, the rate of radical (R0) resection, disease control rate (DCR). This study is registered with Chinese Clinical Trial Registry (ChiCTR2100050410). Results: Between Oct 25, 2021, and Jul 20, 2022, 55 patients were enrolled and received triple therapy (TACE+LEN+CAM). Of these, 37 (67.3%) patients had portal vein tumor thrombosis. Mean tumor diameter for all patients was 112 ± 83 mm. 52 (94.6%) patients with≤2 target lesions, and 3 (5.4%) patients with > 2 target lesions. As of data cutoff on Dec 20, 2022, the median follow-up was 6.7 months (IQR 5.0-9.89). According to modified RECIST criteria, tumor response in patients included complete response to treatment in 9 patients (18.0%), partial response in 27 (54.0%), stable disease in 6 (12.0%), and progressive disease in 7 (14.0%). The ORR was 72.0%, and the DCR was 84.0%. 26 patients underwent surgery after successful conversion therapy. The MPR and pCR rates in the surgery population were 69.2% and 23.1%, respectively. The conversion rate was 55.3% and the R0 resection rate was 100%. 23 (41.8%) of 55 patients had treatment-related adverse event (TRAEs) that were grade 3-5. No grade 3-5 TRAEs occurred after surgery. Conclusions: The triple therapy (TACE+LEN+CAM) significantly improved ORR and the surgical conversion rate of uHCC patients with a manageable safety. Future large-scale randomised trials are warranted. Clinical trial information: ChiCTR2100050410.