OBJECTIVE: To investigate the correlation between secondary pulmonary infection and hepatic encephalopathy (HE) in patients with liver failure and to identify the independent risk factors for HE. STUDY DESIGN: A total of 386 patients with hepatitis B liver failure treated in our hospital from January 2013 to December 2017 were selected as research subjects. They were divided into infection and non-infection groups according to whether the patients had a secondary pulmonary infection. According to the clinical signs, EEG, and number connection test results, the patients were divided into the non-HE group, the subclinical HE group (SHE), and the HE group. Logistic regression analysis was used to evaluate the risk factors of HE in patients with pulmonary infection secondary to liver failure. RESULTS: Smoking history, COPD history, white blood cell (WBC), hemoglobin (HGB), platelet (PLT), serum albumin (ALB), blood urea nitrogen (BUN), serum creatinine (Scr), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood ammonia levels were significantly different between the infection and the non-infection group (p<0.05). The blood ammonia level of patients with HE was significantly higher than that of patients without HE. Secondary pulmonary infection was correlated with the occurrence of SHE and HE. Elderly age, high BUN, high blood ammonia level, combined with upper gastrointestinal bleeding and gastrointestinal infection, were independent factors for predicting the occurrence of HE in patients with pulmonary infection after liver failure. CONCLUSION: Secondary pulmonary infection in patients after liver failure is closely related to the occurrence of HE and is affected by a variety of high-risk factors. This study provides a theoretical basis for individualized treatment and early prevention of HE in patients with liver failure. © Science Printers and Publishers, Inc.