Objective: To investigate and analysis the correlation between the expression levels of serum Interferon-γ (IFN-γ), erythrocyte sedimentation rate (ESR) and soluble interleukin receptor (sIL-2R) in children with acute lymphoblastic leukemia (ALL). Methods: From February 2017 to October 2020, 62 cases of children with acute lymphoblastic leukemia who were diagnosed and treated in the Department of Hematology of our hospital were selected as the ALL group, and the other 62 cases of healthy children who had physical examination in our hospital during the same period were selected as the control group. The serum IFN-γ, ESR, and sIL-2R levels were used to determine the immunophenotype and chromosome analysis of children in the ALL group, followed up the prognosis of the children and given correlation analysis. Results: The proportions of CD34+, CD117+, and karyotype abnormalities in the ALL group were 77.4 %, 58.1 %, 54.8 %, respectively, which were higher than those of the control group (27.4 %, 17.7 %, 14.5 %)(P<0.05). The levels of serum ESR and sIL-2R in the ALL group were higher than those in the control group, and the levels of IFN-γ were lower than those in the control group (P<0.05). In children in the ALL group, followed-up until December 1, 2021, the average follow-up time were 29.14± 4.28 months, the overall survival time were 18.29± 1.22 months, and the event-free survival time were 10.48± 0.33 months; there were 22 cases were died and 40 cases were survived, the mortality rate were 35.5 %. Spearman correlation analysis showed that serum IFN-γ, ESR, sIL-2R levels were correlated with CD34+ positive, CD117+ positive, abnormal chromosomal karyotype, overall survival time, event-free survival time (P<0.05). Multivariate logistic regression analysis showed that IFN-γ, ESR, sIL-2R were important factors affected the prognosis and death of children with acute lymphoblastic leukemia (P<0.05). Receiver operating characteristic curve (ROC) showed that the area under the curve of IFN-γ, ESR, sIL-2R predicted the prognostic death of children with acute lymphoblastic leukemia were 0.867, 0.735, and 0.796, respectively. Conclusion: Children with acute lymphoblastic leukemia are mostly accompanied by high expression of serum IFN-γ and low expression of serum ESR and sIL-2R. All three of them are related to the immune phenotype and chromosome karyotype of the child, and are also the important factors for the prognosis of children. [ABSTRACT FROM AUTHOR]