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To investigate the effects of lenvatinib combined with transcatheter arterial chemoembolization (TACE) on tumor markers apoptotic molecules serum sialic acid transferase 1 (ST6Gal1) angiopoietin-2 (ANG-2) and hepatocyte growth factor(HGF) in patients with unresectable hepatocellular carcinoma. 114 patients with unresectable hepatocellular carcinoma who were admitted to Sichuan Mianyang 404 Hospital from March 2020 to December 2022 were divided into control group (n=57 TACE treatment) and study group (n=57 lenvatinib combine with TACE treatment) by random number table method. The efficacy tumor markers [alpha-fetoprotein (AFP) carbohydrate antigen 199 (CA199) carcinoembryonic antigen (CEA)] serum apoptotic molecules [B-celllymphoma-2-associated X protein (Bax) B-cell lymphoma-2 gene (Bcl-2) survivin (Survivin) cysteine aspartic protease-4 (Caspase-4)]and serum ST6Gal1 ANG-2 HGF levels were compared between two groups and the incidence of adverse reactions during treatment was observed. Compared with control group the total clinical effective rate in study group was higher (P<0. 05). Compared with control group the levels of AFP CA199 and CEA in study group were lower after treatment (P<0. 05). Compared with control group the levels of Bcl-2 and Survivin in study group were lower after treatment and the levels of Bax and Caspase-4 were higher (P<0. 05). Com-pared with control group the levels of ST6Gal1 ANG-2 and HGF in study group were lower after treatment (P<0. 05). There was no difference in the total incidence of adverse reactions between two groups (P>0. 05). Lenvatinib combined with TACE for patients with unresectable hepatocellular carcinoma which can improve the clinical treatment effect regulate the levels of tumor markers, apoptotic molecules and serum ST6Gal1 ANG-2 and HGF with good safety [ABSTRACT FROM AUTHOR]