Objective To explore the correlation between healthcare-associated infection (HAI) and partial indexes in the diagnosis-related groups (DRGs) of patients in thoracic surgery intensive care unit (ICU). Methods DRGs, case mix index (CMI), relative weight (RW), and HAI of patients in thoracic surgery ICU and four subspecialty departments (pulmonary surgery group, esophageal surgery group, mediastinum group [mainly thymic surgery], and trachea group) in a tertiary chest hospital in Shanghai from January to December 2022 were retrospectively analyzed and compared through DRGs index grouping. Results A total of 1 429 patients in the department of thoracic surgery ICU were analyzed, including 59 HAI cases, with a HAI rate of 4.13%. The incidences of HAI in pulmonary surgery group, esophageal surgery group, mediastinum group and trachea group were 3.74% (30/803), 5.84% (25/428), 1.27% (2/157) and 4.88% (2/41), respectively. There was no statistically significant difference in the incidences of HAI among different subspecialty groups (P>0.05). A total of 35 DRGs were involved, with CMI of 2.75, 3.41, 2.35 and 1.25 in pulmonary surgery group, esophageal surgery group, mediastinum group and trachea group, respectively, and RW ranged from 0.53 to 12.62. In the pulmonary surgery group, incidence of HAI in male patients was higher than that in female patients. Higher RW score level was associated with higher incidence of HAI. Differences were all statistically significant (all P < 0.05). Among patients in the esophageal surgery group, the age of HAI group was higher than that of the non-HAI group (P < 0.05). Higher RW score level was associated with higher incidence of HAI (P < 0.05). Among patients in the mediastinum surgery group, the age of patients in the infected group was higher than that in the non-infected group (P < 0.05). Among the 59 HAI cases, 31 were infected with MDROs. Conclusion Focusing on CMI and RW in the DRGs index system, analyzing HAI from the perspectives of disease complexity and overall technical difficulties of medical services can provide reference for the precise management of HAI in the new era.