The objective is to investigate the clinical marker for predicting refractory Mycoplasma pneumoniae pneumonia (RMPP) at early stage, avoiding its progression to severe fulminant cases. A total of 234 enrolled children with Mycoplasma pneumoniae pneumonia (MPP) were divided into the control MPP group and RMPP group from January 2014 to June 2016. Laboratory characteristics were compared between two groups. The prevalence of RMPP was higher in older children (P < 0.001), significantly higher levels of lactate dehydrogenase (LDH), erythrocyte sedimentation (ESR), and C reactive protein (CRP) were found in refractory group compared with the control group (P < 0.01). The area under curve of the multivariate logistic regression model, which sets the categorical variable cutoff levels of CRP, ESR, and LDH based on their receiver operating characteristic curve analysis, is 0.84 with sensitivity 81.6% and specificity 75.7%. Significantly higher positive proportions of urinary alpha1-microglubulin and N-acetyl-beta-glucosaminidase (NAG) were observed in the refractory group than the control group (P < 0.01). A panel combining age and serum levels of LDH >= 302 IU/L, ESR >= 25 mm/h, and CRP >= 15 mg/L might have a considerable clinical value for early prediction of RMPP. Children of RMPP with increased excretion of urinary alpha1-microglubulin and NAG should be concerned.