Abstract: OBJECTIVE To explore the expression levels of serum receptor-interacting protein kinase 1 (RIPK1), C-X-C motif chemokine ligand 8 (CXCL8), and leukocyte differentiation antigen 69 (CD69) in the children with different severities of Mycoplasma pneumoniae pneumonia (MPP) and observe the association with prognosis. METHODS A total of 150 children with MPP who were treated in the Fifth Affiliated Hospital of Southern Medical University from Oct. 2023 to Oct. 2024 were recruited as the research subjects and were divided into the severe group with 68 cases and the mild group with 82 cases according to the illness condition. Meanwhile, 70 healthy children who received physical examination were chosen as the control group based on 1∶1 matching principle. The clinical data were compared among the three groups. The association of the expression levels of RIPK1, CXCL8 and CD69 with the severity of pneumonia was observed by means of generalized additive model (GAM). The values in prediction of illness condition progression was assessed by receiver operating characteristic (ROC) curve. The association of the above indicators with the prognosis was observed. The interactive effect between the illness condition and the prognosis was explored by mesomeric effect model. RESULTS There were significant differences in RIPK1, CXCL8 and CD69 among the children with different severities of MPP(P＜0.05). GAM analysis showed that there were significant differences in the associations between the RIPK1, CXCL8, CD69 levels and the severity of disease(P＜0.05). ROC curve analysis indicated that the three indicators had high value in prediction of MPP condition, and the joint detection of the three indexes had the highest predictive value(P＜0.05). There was intermediate regulatory effect between the severity of pneumonia and the prognosis of the children(P＜0.05). CONCLUSION RIPK1, CXCL8 and CD69 can reflect the severity of MPP in the children and have intermediary regulatory effect on the association of illness condition with prognosis.