Update publication information. Ubiquitination plays a critical role in human cancer genesis and metastasis, but how the systemic ubiquitinome changes during these processes remains unclear. In this study, our dataset of approximately 12,000 identified ubiquitinated sites provided valuable insight into human hepatocellular carcinoma (HCC). We found that both the ubiquitinated sites and ubiquitin chains were obviously increased in HCC, thereby suggesting ubiquitination was related to tumorigenesis. The ubiquitination of proteins involved in antigen processing and presentation occupied a vital position in HCC genesis. Moreover, during the progression of HCC metastasis, we discovered increased ubiquitinated sites with shorter ubiquitin chains, which might have resulted from monoubiquitination and revealed the key role of ubiquitination on proteins involved in cell-cell adhesion.