Six6, along with Dachous (Dach) proteins, promoted cell proliferation by directly repressing the expression of cyclin-dependent kinase inhibitors (Li et al., 2002; Iglesias et al., 2014) while Six4 regulated the expression of Yap1 and c-Met to promote cell proliferation in HCC (He et al., 2020). Here, SIX4 is linked to hepatocellular carcinoma.