Objective To investigate the correlation between serum heparin-binding protein (HBP) and other clinical indicators with the bronchoscopic lesion severity in children with Mycoplasma pneumoniae pneumonia (MPP), in order to understand their potential value in guiding diagnosis and treatment. Methods A retrospective analysis was conducted on 248 children with acute MPP admitted to the Department of Pediatrics, Affiliated Hospital of Xuzhou Medical University from December 2023 to September 2025. Patients were divided into severe lesion group (n=96) and mild lesion group (n=152) based on bronchoscopic findings. Clinical data including fever peak and duration, serum levels of HBP, C-reactive protein (CRP), D-dimer (DD), lactate dehydrogenase (LDH), and neutrophil percentage (N%) were collected. Statistical analyses were performed between groups, followed by correlation analysis between HBP levels and significant clinical indicators. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of HBP and other indicators for bronchoscopic lesion severity. Results HBP levels in the severe lesion group were significantly higher than those in the mild lesion group (median: 36.2 ng/mL vs 22.8 ng/mL, P<0.001). The severe lesion group also exhibited higher peak fever, longer fever duration, and elevated CRP, DD, and LDH levels (all P<0.05). HBP showed positive correlations with fever duration, CRP, DD, LDH, and N% (r_s =0.256, 0.302, 0.635, 0.327, 0.140, respectively; all P<0.05). ROC analysis demonstrated that HBP had the highest area under the curve (AUC=0.850) for predicting bronchoscopic lesion severity, followed by DD (AUC=0.832), CRP (AUC=0.784), LDH (AUC=0.780), fever duration (AUC=0.681), and N% (AUC=0.642). At a cut-off value of 28.9 ng/mL, HBP predicted severe lesions with 80.2% sensitivity and 79.6% specificity. Conclusions Serum HBP, CRP, DD, and LDH are significantly associated with the microscopic severity of bronchoscopic lesions in children with MPP. HBP shows superior predictive performance and may provide valuable clinical guidance for assessing lesion severity.