Background: Approximately 64% of Chinese patients with HCC were evaluated as China Liver Cancer Stage (CNLC) II/III tumors, equivalent to Barcelona Liver Cancer Stage (BCLC) B or C. The conversion of an initially unresectable HCC (uHCC) to a resectable HCC may be an optimal approach to achieve better outcomes. Although donafenib, camrelizumab and transarterial chemoembolization (TACE) were recommended for uHCC in Chinese guidelines, the effect of these agents in the pre-operative setting was unclear. The present study was to assess the feasibility and safety of donafenib plus camrelizumab with TACE as conversion therapy in patients with uHCC. Methods: Patients were enrolled if they were aged 18 to 70 with primary CNLC stage IIb/IIIa uHCC, Child-Pugh classification A or B (≤7 points) and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. The patients received donafenib (100 mg po Bid), camrelizumab (200 mg iv Q3W) and TACE for up to 4 cycles (usually 2 cycles, increased to 3 or 4 cycles if necessary), followed by investigator assessment. The primary endpoint was the rate of major pathologic response (MPR), defined as ≤10% residual viable tumor in postoperative specimens. The secondary endpoints were the R0 resection rate, event-free survival (EFS), objective response rate (ORR) and disease control rate (DCR) by mRECIST criteria, and safety. Results: Sixteen patients, 11 men (68.8%) and five women (31.2%), of median age 58 years (range 49-70 years) were enrolled from May 2021 to July 2022. At the data cut-off (November 2022), one patient was still awaiting surgery, whereas 12 (80.0%) of the remaining 15 patients were successfully converted to resectable. Of the 12 patients who underwent successful hepatectomy (R0 resection), 6 (50%) achieved MPR. Based on mRECIST criteria, the ORR was 81.3%, and the DCR was 93.8%. Median EFS was 9.0 months (95%CI 7.1-10.9 months). Most treatment-related adverse events (TRAEs) were grade 1-2. Grade 3 TRAEs occurred in 4 patients. No patient experienced a Grade 4 or 5 TRAE. Conclusions: These preliminary results suggested that conversion therapy with donafenib, camrelizumab and TACE was safe and effective for uHCC. Clinical trial information: ChiCTR2100043462.