Background: Serum amyloid P-component (SAP) contributes to the clearance of apoptotic cells. As one of the main acute-phase reactants, SAP regulates key aspects of inflammation and sets a threshold for immune cell activation. This study aimed to investigate the association of SAP levels with symptomatic lung toxicities after thoracic radiotherapy (TRT) and overall survival (OS) in non-small lung cancer (NSCLC) patients. Methods: The SAP level at diagnosis and during TRT was evaluated by ELISA in 113 clinically inoperable NSCLC patients. Data of radiation pneumonitis (RP)/lung fibrosis, and OS were recorded. Results: The mean SEM values of SAP levels at baseline, week 2, and week 4 during TRT were 83.8 +/- 6.4, 36.7 +/- 4.8, and 36.5 +/- 3.4 mu g/mL, respectively (p < 0.0001). Using the median value (83.0 mu g/mL) as a cutoff, patients with higher baseline SAP level had longer OS than those with lower SAP level (58.2 vs. 23.1 months, p = 0.044). Baseline SAP level, gender, pathology and BED10 were significantly associated with OS in univariate analysis, while only baseline SAP level, pathology, and BED10 were found to be prognostic for OS in multivariate analysis. Patients with symptomatic RP had lower SAP levels than those with no or mild RP (82.7 +/- 7.3 vs. 96.8 +/- 4.8 ttg/mL, p = 0.024). Conclusions: The baseline SAP level can be used to predict symptomatic radiation pneumonitis and was prognostic for survival after TRT for NSCLC patients.