Small ubiquitin-like modifiers (SUMO) are highly conserved post-translational modification proteins that are present in eukaryotic cells. They are extensively expressed in diverse tissues, including the heart, liver, kidney, and lungs. SUMOylation, a crucial post-translational modification, exhibits a strong effect on DNA repair, transcriptional regulation, protein stability and cell cycle progression. Increasing evidence has demonstrated that SUMOylation is closely related to the development of liver disease. Therefore, the effects of SUMOylation in liver diseases, such as Hepatocellular carcinoma (HCC), viral hepatitis, non-alcoholic fatty liver disease (NAFLD), cirrhosis and primary biliary cirrhosis (PBC) were reviewed in this study. Specifically, SUMO1 was found to promote the invasion and metastasis of HCC and may promote hypoxia-mediated P65 nuclear transport while accelerating the progression of HCC. In addition, SUMO1-modified centrosomal P4.1-associated protein (CAPA) was observed to be overexpressed in Hepatitis B virus (HBV)-related HCC in response to TNF-α stimulation. Furthermore, SUMOylated CAPA was found to induce HBX-triggered NF-κB activation. Considering the diversity and significance of SUMOylation, targeting of the SUMOylation pathway may serve as an effective approach in the treatment of liver diseases.