Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. Affected patients have poor prognoses due to high rates of post-surgical recurrence and metastasis. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) reportedly contributes to the development and progression of various human cancers. Thus far, there have been no comprehensive studies regarding the expression of BAMBI in HCC; similarly, no studies have investigated the prognostic significance of BAMBI and its associated mechanisms in HCC. In this study, we analyzed the expression profiles of BAMBI, along with its contributions to pathological findings, metastasis characteristics, and prognosis, in multiple human cancers. We found that upregulation of BAMBI was associated with poor prognosis in HCC. Next, we explored the associations of BAMBI with multiple cell signaling pathways, immune cells, and immune checkpoints in HCC. The results showed that BAMBI was associated with tumor proliferation, epithelial-mesenchymal transition (EMT) markers, glycolysis, fatty acid biosynthesis and degradation pathways, and immune checkpoint regulation in HCC. In vitro and in vivo experiments showed that BAMBI promoted polarization of M1 macrophages and is linked to the expression of key genes involved in glycolipid metabolism. Furthermore, protein-protein interaction analysis suggested that BAMBI plays multiple roles in HCC by regulating genes in the transforming growth factor (TGF)-β and Wnt signaling pathways. Our findings elucidated that BAMBI is a prognostic biomarker and is associated with macrophage polarization, glycolysis, and lipid metabolism in HCC.