Abstract: Objective To research the risk factors for nosocomial infection and death in patients with sepsis and provide reference for the rapid diagnosis and early treatment of sepsis. Methods A total of 74 patients with sepsis admitted to hospital from January, 2014 to June, 2015 were collected to analyze the relationship between nosocomial infection and mortality in 22 related factors. Results Nosocomial infection in sepsis patients was related to 11 risk factors:age, septic shock, APACHE score ≥ 20 points, SOFA score ≥ 2 points, duration of operation, use of corticosteroids, central venous catheterization, more than three catheterizations, more than 2 kinds of bacterial infection, duration of infection ≥ 5 d and et al. Mortality of patients was associated with 12 risk factors:diabetic history, septic shock, APACHE score ≥ 20 points, SOFA score ≥ 2 points, blood sugar ≥ 8.3 mmol/L, duration of operation ≥ 3 h, more than three catheterizations, more than 2 kinds of bacterial infection, duration of infection< 5 d, hospital stay < 20 d and et al. Septic shock, APACHE score ≥ 20 points, SOFA score ≥ 2 points, more than three catheterizations, more than 2 kinds of bacterial infection were the common risk factors of nosocomial infection and death of patients with sepsis. The patients with the above 5 factors should be transferred to the ICU for intensive treatment. Conclusion The patients with 5 common risk factors (Septic shock, APACHE score ≥ 20 points, SOFA score ≥ 2 points, more than three catheterizations, more than 2 kinds of bacterial infection) should be paid more attentions on their treatment to improve the prognosis. If APACHE score ≥ 20 points and SOFA score ≥ 2 points, anti-infective therapy should be performed immediately, and start the standard process for the treatment of sepsis. Most of sepsis patients died less than 5 days after infection, the early diagnosis and treatment is very important for the prognosis of sepsis.