Objective To investigate the incidence and economic burden of healthcare-associated infection (HAI) in patients after liver transplant. Methods Basic clinical information, infection status, and related medical expenses of liver transplant patients in the department of hepatobiliary surgery in a tertiary first-class hospital from November 2012 to December 2023 were investigated retrospectively. A case-control study design was employed, with post-li-ver transplant patients who developed HAI as the infection group and those without HAI during the same period as the control group. The 1∶1 propensity score matching (PSM) method was adopted (caliper value was set at 0.05, employing sampling without replacement). Length of hospital stay and hospitalization expenses between patients in the infection group and the control group were compared using Wilcoxon rank-sum test, and the economic burden due to HAI was calculated. Results A total of 336 liver transplant patients were included in study, out of which 48 had HAI, with an incidence of 14.29%. 44 pairs were successfully matched by PSM. After matching, the median hospitalization expense for patients in the infection group was 334 473.73 Yuan, while that of the control group was 285 824.82 Yuan, with a statistically significant difference (Z=-3.430, P<0.05). The direct economic burden of[LM]HAI in liver transplant patients was 48 648.91 Yuan. After matching, the median length of hospital stay in the infection group (37.0 days) was 12.5 days longer than that in the control group (24.5 days), with statistically significnat difference (Z=-3.630, P<0.001). Conclusion HAI after liver transplant increases patients’ hospitalization expense and prolongs their hospital stay, thus brings huge economic burdens to the patients.