Background <p>We aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) plus tyrosine-kinase inhibitors (TKIs) with or without programmed death-1 (PD-1) inhibitors in recurrent intermediate-advanced hepatocellular carcinoma (HCC).</p> Materials and methods <p>In this retrospective, single-center cohort study (January 2016-January 2024), 39 consecutive patients with recurrent HCC (BCLC B/C) received TACE combined with (1) regorafenib (<i>n</i> = 14), (2) lenvatinib + PD-1 inhibitor (<i>n</i> = 12), or (3) regorafenib + PD-1 inhibitor (<i>n</i> = 13). Overall survival (OS) and progression-free survival (PFS) were primary outcomes. Objective response rate (ORR) and disease control rate (DCR) were secondary. Multivariable Cox regression and propensity score matching analyses were performed. A post-hoc power analysis was conducted to quantify statistical power.</p> Results <p>Median follow-up was 36.5 months. Median OS and PFS for the entire cohort were 42.9 months (95% CI 27.1–58.7) and 16.5 months (95% CI 13.6–19.5), respectively. No significant differences in OS (<i>P</i> = 0.164) or PFS (<i>P</i> = 0.830) were observed among the three groups. ORR was 12.8% and DCR 51.3%. BCLC stage B (vs. C) was an independent favorable prognostic factor for OS (HR 0.03, <i>P</i> = 0.01) and PFS (HR 0.04, <i>P</i> = 0.038). Grade ≥ 3 adverse events occurred in 2 (5.1%) patients. The median number of TACE sessions was 4 (IQR 3–6) for Group A, 5 (IQR 3–7) for Group B, and 4 (IQR 3–5) for Group C (<i>P</i> = 0.72).</p> Conclusion <p>TACE plus TKIs with or without PD-1 inhibitors showed acceptable efficacy and safety in recurrent intermediate-advanced HCC. The addition of PD-1 inhibitors did not demonstrate additional survival benefit in this small cohort. However, the present sample size was underpowered to detect a clinically meaningful but modest survival difference. Prospective randomized trials are warranted.</p>