In summary, our study clearly documents the following regarding IGFBP3: i) it is downregulated in a high proportion of pediatric liver tumors; ii) it is epigenetically silenced in a subset of HB, indicating that additional repressive mechanisms must exist for this gene; iii) promoter methylation is a late event and predominantly occurs in progressed metastatic and vessel-invasive HB, which may be of clinical significance for HB patients by proposing adapted therapies; and iv) it prevents the migration and invasiveness of HB. This evidence concerns the gene IGFBP3 and Neoplasm of the liver.