Objective To investigate the application value of serum IL-6, PCT and Hs-CRP combined detection in the grade prediction of mycoplasma pneumoniae disease in children. Methods 158 children with MP admitted to our hospital from May 2021 to May 2024 were retrospectively collected as MP group. Patients in MP group were divided into mild MP group (n=85) and severe MP group (n=73) according to clinical pulmonary infection score (CIPS). Another 150 children who underwent physical examination in our hospital during the same period were selected as the control group. Serum levels of IL-6, PCT and Hs-CRP were detected. The serum levels of IL-6, PCT and Hs-CRP were compared between the two groups. The serum levels of IL-6, PCT and Hs-CRP in children with different disease grades of MP were compared. ROC curve was plotted and AUC was calculated to evaluate the predictive value of serum IL-6, PCT and Hs-CRP for the disease grade of children with MP. Results Compared with control group, the serum levels of IL-6, PCT and Hs-CRP in observation group were significantly increased (P < 0.05). Serum levels of IL-6, PCT and Hs-CRP in mild MP group and severe MP group were significantly increased (P < 0.05). The AUC (95%CI), sensitivity and specificity of combined detection of serum IL-6, PCT and Hs-CRP were 0.921 (0.876 to 0.956), 92.00% and 90.00%, respectively, which were significantly higher than that of single detection of serum IL-6, PCT and Hs-CRP (P < 0.05). Conclusion The combined detection of serum IL-6, PCT and Hs-CRP has high application value in the grade prediction of MP disease in children, which can not only sensitively reflect the inflammatory state of the body, but also accurately distinguish the different severity of MP infection.