Acute Radiation Pneumonitis (ARP) is one of the most common dose-limiting toxicities of thoracic radiotherapy. The accurate diagnosis of ARP remains a challenge because of the lack of a rapid biomarker capable of differentiating ARP from bacterial pneumo (BP). The aim of this study was to investigate the potential usefulness of procalcitonin (PCT) in the differential diagnosis of ARP and BP. Lung cancer patients who had undergone thoracic radiotherapy within 6 months and were admitted to hospital for ARP or BP were retrospectively analyzed. The serum levels of PCT, C-reactive protein (CRP) and white blood cells (WBC) were compared between the two groups. Receiver operating characteristic (ROC) curve was used to assess the diagnostic value of PCT, CRP and WBC in the differential diagnosis of ARP and BP and determine the best cut-off values. One hundred eighteen patients were included. Among them, seventy-seven patients were diagnosed with ARP, and 41 patients were diagnosed with BP. The PCT concentrations for patients diagnosed with ARP group were significantly lower than those in the BP group (P < 0.001). There were no differences in CRP and WBC between the two groups. The areas under the ROC curves (AUC) for PCT, CRP and WBC were 0.745, 0.589 and 0.578, respectively. The best cutoff values of PCT, CRP and WBC were 0.47 μg/L, 54.5 mg/L and 9.9 × 109/L, respectively. Low serum PCT levels are associated with ARP. PCT is a useful biomarker to distinguish ARP from BP.