Background <p>Systemic therapy combined with local intervention has demonstrated promising efficacy in patients with Unresectable hepatocellular carcinoma (uHCC). Bevacizumab plus sintilimab combined interventional treatment (BSIT) and lenvatinib plus sintilimab combined interventional treatment (LSIT) are widely used in clinical practice in China, but the optimal option remains unclear. This study aimed to compare the efficacy and safety of BSIT and LSIT in intermediate and advanced uHCC.</p> Methods <p>Primary endpoints were progression-free survival (PFS) and objective response rate (ORR); secondary endpoints included overall survival (OS), disease control rate (DCR), and treatment-related adverse events (TRAEs). Propensity score matching (PSM) was applied to reduce bias. Kaplan–Meier and multivariable Cox analyses were used to assess survival and prognostic factors.</p> Results <p>After PSM, 160 patients were assigned to BSIT (<i>n</i> = 80) and LSIT (<i>n</i> = 80). Survival outcomes, ORR, and DCR were similar between groups. Grade 3/4 AEs were comparable, except gastrointestinal bleeding, which was higher in BSIT. No grade 5 events occurred. Multivariate analysis revealed that extrahepatic metastasis and number of intrahepatic lesions independently predicted progression-free survival, while ECOG performance status was associated with overall survival.</p> Conclusions <p>Sintilimab plus lenvatinib or bevacizumab with interventional therapy showed comparable efficacy and tolerable safety in intermediate–advanced uHCC.</p>