OBJECTIVE: The present study aims to explore the correlation of the transforming growth factor ß (TGF-ß), drosophila mothers against decapentaplegic protein gene (SMAD) 2/3/4, and leukemia inhibitory factors (LIF) with the cyst formation of hepatic Echinococcus granulosus in young children. METHODS: A total of 40 patients who met the diagnostic criteria for children's hydatid disease in people's Hospital of Xinjiang Uygur Autonomous Region between January 2020 and June 2021 were enrolled a s the study subjects. The cystic fluid of these children was collected as the case group and the corresponding infected viscera or pericystic tissue as the control group, with 40 cases in each group. In vitro cultured protoscolice of hydatid cyst, four groups including control group, LIF siRNA group, LIF factor group and SMAD4 siRNA group were divided by inhibiting TGF-ß/SMADs signal pathway. Each assay was performed in triplicate. The expression of TGF-ß, SMAD2/3/4 and LIF were detected. RESULTS: The results of the clinical trial showed that the contents of SMAD2 and SMAD3 were increased in the case group compared with the control group; the differences were statistically significant (P < 0.05). The expression levels of TGF-ß, Smad4, and LIF increased in the case group compared with the control group; however, the differences were not statistically significant. The results of further in vitro experiments, the expression levels of TGF-ß, SMAD 2/3/4, and LIF after adding siRNA to interfere with Smad4 decreased in the case group compared with the control group; the differences were statistically significant (P < 0.05). Compared with the control group, the expression levels of TGF-ß, SMAD2/3/4, and LIF increased after treatment with added LIF in the case group, and the expression levels of TGF-ß, SMAD2/3/4, and LIF decreased after adding siRNA to interfere with LIF in the case group; the differences were all statistically significant (P < 0.05). CONCLUSION: SMAD2 and SMAD3 have a certain clinical relevance with hydatidosis in young children. The LIF expression level may be related to the cystic transformation of protoscoleces. It has been suggested that the TGF-ß/Smads/LIF signaling pathway may be present in the process of protoscoleces cyst formation; this provides a research basis for the prevention and treatment of post-infection parasitism of E. multilocularis eggs in young children.