In this review, we will focus on the role of the Homeobox genes in the generation of HCC, including tumor-initiating stem-like cells (TICs), epithelial to mesenchymal transition (EMT), immunotolerance, and viral infection (Figure 1), and list the promoting or repressing function of Homeobox genes in HCC (Table 1 and Table 2). This evidence concerns the gene LBX1 and hepatocellular carcinoma.