High rate of recurrence impaired the prognosis of hepatocellular carcinoma (HCC) after surgery. We aimed to explore the safety and efficacy of neoadjuvant drug-eluting bead transarterial chemoembolization (D-TACE) and tislelizumab therapy for resectable or borderline resectable HCC.41 HCC patients received neoadjuvant therapy and surgery were respectively enrolled. The safety and efficacy of the neoadjuvant therapy were assessed. The prognosis was evaluated and compared with that of 41 matched HCC patients who received surgery alone.36 (87.8%) patients had adverse events (AEs) and only one patient had a grade 3/4 of ALT elevated. All patients performed surgery successfully and no severe postoperative complications occurred. The objective response rate (ORR) was 56.1% and 87.8% based on RECIST 1.1 and mRECIST, respectively. 15 (36.6%) patients had radiological complete tumor necrosis and the disease control rate (DCR) was 100%. The pathological complete response (pCR) and major pathological response (MPR) was 13 (31.7%) and 18 (43.9%), respectively. The incidence of microvascular invasion (MVI) was 4.9% in neoadjuvant therapy patients, compared with 64.9% before propensity score matching (PSM) and 60.9% after PSM for surgery alone patients. Neoadjuvant therapy patients had a significant better prognosis than surgery alone patients (recurrence-free survival p = 0.041, overall survival p = 0.006).Our preliminary results suggest the neoadjuvant D-TACE and tislelizumab therapy is safe and benefit to the pathological results and prognosis for patients with resectable or borderline resectable HCC.© 2023 Published by Elsevier Ltd.