The objective of the present study was to explore the role of hepatocyte growth factor (HGF) in directing treatment of Mycoplasma pneumoniae pneumonia (MP). Serum levels of HGF were assessed using ELISA in 65 pediatric patients with MP, 42 with bacterial pneumonia and 30 healthy controls. Serum levels of C-reactive protein (CRP), the standard guide for MP treatment, were also examined in severe and non-severe MP. The sensitivity and specificity of HGF and CRP in assessing the outcome of azithromycin treatment of MP were compared using receiver operating characteristic curves. HGF levels were elevated in MP and bacterial pneumonia patients compared with healthy controls. HGF levels were also significantly higher in severe MP than in non-severe MP. HGF showed higher sensitivity and specificity than CRP in assessing outcomes of azithromycin treatment of MP. The results of the present study indicated that HGF may be used to detect severe MP and to direct its management. Furthermore, HGF may be better predictive marker to assess the effectiveness of azithromycin treatment of MP than CRP.