Objective To analyze the prognostic factors in acute-on-chronic liver failure ( ACLF) patients with hepatic encephalopathy ( HE) and to explore the risk factors for prognosis. Methods A retrospective analysis was performed on106 ACLF patients with HE who were hospitalized in our hospital from January 2010 to July 2013. The patients were divided into improved group and deteriorated group. The univariate indicators including age, sex, laboratory indicators [total bilirubin ( TBil) , albumin ( Alb) , alanine aminotransferase ( ALT) , aspartate amino-transferase ( AST) , and prothrombin time activity ( PTA) ], the stage of HE, complications [persistent hyponatremia, digestive tract bleeding, hepatorenal syndrome ( HRS) , ascites, infection, and spontaneous bacterial peritonitis ( SBP) ], and plasma exchange were analyzed by chi-square test or t-test. Indicators with statistical significance were subsequently analyzed by binary logistic regression. Results Univariate analysis showed that ALT ( P = 0. 009) , PTA ( P = 0. 043) , the stage of HE ( P = 0. 000) , and HRS ( P = 0. 003) were significantly different between the two groups, whereas differences in age, sex, TBil, Alb, AST, persistent hyponatremia, digestive tract bleeding, ascites, infection, SBP, and plasma exchange were not statistically significant ( P >0. 05) . Binary logistic regression demonstrated that PTA ( b =-0. 097, P =0. 025, OR =0. 908) , HRS ( b =2. 279, P =0. 007, OR =9. 764) , and the stage of HE ( b = 1. 873, P = 0. 000, OR = 6. 510) were prognostic factors in ACLF patients with HE. Conclusion The stage of HE, HRS, and PTA are independent influential factors for the prognosis in ACLF patients with HE. Reduced PTA, advanced HE stage, and the presence of HRS indicate worse prognosis.