In recent years, studies have demonstrated that the gut microbiome may play an important role in hepatobiliary and pancreatic malignancies. In this article, the authors address the association of the gut microbiome with hepatocellular carcinoma, cholangiocarcinoma and pancreatic cancer, and the research progress of the gut microbiome in the treatment of hepatobiliary and pancreatic malignancies, so as to discuss the application value of the gut microbiome in clinical treatment of hepatobiliary and pancreatic malignancies.