PURPOSE: The aim of this systematic review and meta-analysis is to determine the efficacy and safety of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) combined with immune checkpoint inhibitors (ICIs) in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We systematically searched Embase, Cochrane Central Register of Controlled Trials, Pubmed/Medline, and Web of Science from inception to September 10th of 2024 for studies published with the following medical subject heading terms: "selective internal radiation therapy", "immunotherapy", "immune checkpoint inhibitors", and "hepatocellular carcinoma". In addition, the references of included studies and systematic reviews were evaluated for additional studies. The outcomes of interest were median overall survival (mOS), median progression-free survival (mPFS), median time to tumor progression (mTTP), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). A subgroup analysis of ORR was conducted based on patients' BCLC staging, along with a comparison between studies that initiated ICIs prior to SIRT and those that administered SIRT before ICIs. RESULTS: The review included seven studies, consisting of four clinical trials and three retrospective cohort studies, with a total of 184 patients. The pooled analysis demonstrated an ORR of 58.08% (95% CI: 39.07-77.09) and a DCR of 85.03% (95% CI: 76.23-93.83). The pooled mTTP, mPFS and mOS resulted in 7.17 months (95% CI: 5.05-9.29), 7.12 months (95% CI: 5.29-8.95) and 20.43 months (95% IC: 17.58-23.29), respectively. The subgroup analysis of ORR according to the patients' BCLC staging, including BCLC-B and BCLC-C, resulted in a pooled ORR of 75.71% (95% CI: 57.71-93.71) and 60.86% (95% CI: 37.10-84.63), respectively, with no significant difference between groups (p = 0.33). There was no significant difference in the subgroup analysis between studies that initiated ICIs prior to SIRT and those that administered SIRT before starting ICIs. During treatment 53.48% (95% CI: 25.89-80.06) of the patients experienced grades 1-2 adverse events, and 16.17% (95% CI: 6.52-28.52) experienced grades 3-4 adverse events. One patient in the analysis experienced a grade 5 adverse event. CONCLUSION: The findings of this systematic review and meta-analysis indicate that the combination of SIRT using Y-90 with ICIs may offer a durable treatment response and promising efficacy with an acceptable safety profile for HCC. However, results should be interpreted with caution due to the limited number of published studies and the need for further investigation regarding patient selection, treatment sequence, efficacy, and safety.