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Background: Microballoon interventions (MBIs) have been proposed as useful tools to improve the efficacy of locoregional liver treatments. The aim of this systematic review was to summarize the existing evidence on procedural characteristics, safety, and efficacy of MBIs. Methods: PubMed and Cochrane Central Register of Controlled Trials were queried for original research articles evaluating MBIs in patients with liver malignancies from 2012 to August 2022. Search terms employed were liver malignancies, hepatocellular carcinoma, cholangiocarcinoma, liver metastases, microballoon transarterial chemoembolization, balloon-occluded trans-arterial chemoembolization, balloon-occluded selective internal radiation therapies, balloon-occluded TACE and ablation, and safety or oncological results or efficacy. Merely technical studies and animal studies were excluded. Results: Thirty-four original research studies and one abstract involving 744 patients treated with MBIs were included; 76% of the studies were retrospective, with low risk of bias and moderate-to-poor levels of evidence. Heterogeneity precluded meta-analysis. All studies proved MBI safety, which was not inferior to non-occlusive procedures. Balloon employment ameliorates oncological results, improving time to recurrence, objective response rate, and lowers need for retreatment. Conclusions: MBIs appear to be potential game changers in the treatment of liver malignancies. Multicentric, prospective and randomized studies are necessary to confirm these findings. Full article