Given that HCC is primarily linked to HBV and HCV, and IGF‐II is recognized as a serum marker for human HCC, it has been observed that O‐GlcNAc modification of IGFBP‐6 at Ser204, induced by HCV/HBV infection, reduces its binding with IGF‐II, leading to increased cellular expression of IGF‐II and the advancement of HCC. This evidence concerns the gene IGFBP6 and hepatocellular carcinoma.