Abstract: Objective To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) versus TACE alone in patients with recurrence after radical resection of hepatocellular carcinoma. Methods Patients who were admitted to the Affiliated Hospital of Xuzhou Medical University and underwent radical resection for hepatocellular carcinoma from April 2018 to August 2023 were enrolled and their clinical data were retrospectively analyzed. The patients were divided into two groups: a recurrence group (n=94) and a non-recurrence group (n=90). Furthermore, those in the recurrence group were divided into two groups: a TACE+TKI group (receiving TACE combined with TKIs, n=68), and a TACE treatment group (receiving TACE alone, n=26). After treatment, patients were followed up for short-term efficacy, progression-free survival (PFS) and safety. Results A total of 184 patients were enrolled in this study, including 94 patients in the recurrence group and 90 patients in the non- recurrence group, as well as 64 patients in the TACE+TKI group and 26 patients in the TACE group. The TACE+TKI group showed higher objective response rate (ORR) than the TACE group, with statistical difference (54.1% vs. 34.6%, P＜0.01). The TACE+TKI group showed higher disease control rate (DCR) than the TACE group, with statistical difference (82.3% vs 57.7%, P<0.001). The median PFS was 29.9 months for the TACE+TKI group and 7.94 months for the TACE group. No grades 4-5 adverse events occurred in the TACE+TKIs group and the TACE group, and the adverse events that did occur were controllable. Conclusions Compared with TACE treatment alone, TACE combined with TKIs can improve PFS and DCR in patients with postoperative recurrence, with fair safety, which is expected to benefit patients with postoperative recurrence of hepatocellular carcinoma.