〔Abstract〕 SMYD5 is a ribosomal methyltransferase with SET and MYND structural domains, which is a member of the SMYD family and is expressed in a variety of tissues, including ovary and testis. This enzyme participates in biological processes such as gene expression regulation, cell development and differentiation, and maintenance of genomic stability through ribosomal protein methylation modification. In recent years, research on SMYD5 has increased in cancers including hepatocellular carcinoma, gastric adenocarcinoma, and lung cancer. Studies have revealed that SMYD5 exhibits high expression levels in various diseases including hepatocellular carcinoma, gastric adenocarcinoma, lung cancer, and inflammatory bowel disease, influencing the progression of these conditions. This review summarizes the role of SMYD5 in hepatocellular carcinoma, inflammatory bowel disease, and other biological functions, aiming to provide a reference for related disease research.