Abstract: Objective To study the effect of antibiotics prophylaxis on nosocomial infection in liver cirrhotic patients with acute upper gastrointestinal hemorrhage so as to provide basis for the clinical treatment. Methods From January 2012 to December 2013, 180 cases with liver cirrhosis combined with upper gastrointestinal bleeding were selected as the research objects. All the patients were randomly divided into the ceftriaxone sodium group (60 cases), levofloxacin group (60 cases) and control group (60 cases); the control group without antibiotics. The rates of nosocomial infection and re-bleeding, the mortality were observed and compared. Results The rate of nosocomial infection and the rate of re-bleeding in Ceftriaxone sodium group were 8.33% and 8.33% respectively and it was better than the control group (P<0.05). The rate of nosocomial infection and the rate of re-bleeding in Levofloxacin group were 10.0% and 6.67% respectively and it was better than the control group (P<0.05). The rate of nosocomial infection and re-bleeding had no statistical significance between the two antibiotics groups. There was no statistical difference between the mortality (5.0% vs 3.33% vs 8.33%) in three groups. Conclusion The preventing use antibiotics on cirrhotic patients with upper gastrointestinal hemorrhage can reduce the rates of nosocomial infection and re-bleeding with significant value in clinical application.