To detect the expression of inflammatory factors such as interleukin-1β (IL-1β), interleukin-6 (IL-6), transforming growth factor (TGF-β), and tumor necrosis factor (TNF-α) in the tumor tissue of ventricular septal defect (VSD) in congenital heart disease and to explore the role of inflammatory response in the formation of aneurysmal perimembranous VSD(APVSD). Children with APVSD of congenital heart disease treated by surgery were selected and divided into true aneurysmal perimembranous group (TAP group) and pseudoaneurysmal perimembranous group (PAP group) according to echocardiography and surgical findings. There were 15 children in the TAP group and 31 in the PAP group. The aneurysmal perimembranous tissue of the two groups of children was collected during the operation. IL-1β, IL-6, TGF-β, and TNF-α were positively expressed in the aneurysmal perimembranous tissue of the two groups, and the expression levels of all inflammatory factors in the PAP group were higher than those in the TAP group, and the difference was statistically significant (
P
<
0.05
). The expression levels of IL-1β, IL-6, TGF-β, and TNF-α in the aneurysmal perimembranous tissue of the two groups were negatively correlated with the width of the APVSD breach. IL-1β, IL-6, TGF-β, and TNF-α may be involved in the occurrence and development of APVSD through inflammatory mechanism.