Update datafiles Update publication information. Ubiquitination plays a critical role in human hepatocellular carcinoma (HCC) genesis and metastasis, but how these processes affect systemic ubiquitinome still remains unclear. In this study, our dataset of around 12,000 diGly modified sites was identified providing a valuable insight into HCC. We find both the diGly sites and ubiquitin chains undergo bulk increase in HCC, suggesting the boost of diGly modification activities in tumor genesis. Two of the most significant alterations of ubiquitination modification in HCC concern components of proteasome and antigen presentation activity. Moreover, during the progression of HCC metastasis, we discover a more extensive diGly modified sites with shorter ubiquitin chains and reveal the key role of ubiquitination modification on proteins involving cell-cell adhesion.