Due to persistent systemic inflammation and immunosuppressive conditions, patients with liver cirrhosis are susceptible to bacterial infection, which may progress to sepsis without proper control. Early effective antibiotic therapy is the key to improving the prognosis of patients with sepsis. This article briefly describes the pathophysiological mechanism of sepsis in patients with liver cirrhosis and the current status of the diagnosis and treatment of sepsis, and it is pointed out that metagenomic next-generation sequencing can be used to guide effective antibacterial treatment of sepsis.