Objective To explore the direct economic loss due to healthcare-associated infection(HAI) in patients with liver failure, so as to make policy makers and health care workers have an intuitive understanding of the harm of HAI. Methods Patients with liver failure in a tertiary first-class general hospital in Guizhou Province from December 2009 to December 2014 were analyzed, according to 1:1 ratio, patients with HAI were in case group, while those without HAI during the same period were in control group, length of hospital stay and medical cost were compared by paired rank sum test, SPSS 17.0 software was used to perform statistical analysis. Results 276 cases of liver failure were collected, 23 of which were matched effectively. The results showed that the average length of hospital stay of liver failure patients complicated with HAI was 11 days longer than that of patients without HAI (P=0.01), and the average medical cost were 22 980.01 yuan more (P=0.01). The top three cost in case group from high to low were medicine (40.25%), material (20.32%) and blood transfusion (13.90%), in control group were medicine (60.13%), laboratory detection (14.57%) and blood transfusion (7.25%). Conclusion The average length of hospital stay of liver failure patients complicated with HAI is longer than that of patients without HAI, and the average medical cost is higher, which increases the economic burden of patients.