We measured various biomarkers in non-small-cell lung cancer (NSCLC) patients in an effort to discover novel prognostic indicators. We identified three such markers, namely platelet-derived microparticles (PDMP), plasminogen activator inhibitor (PAI)-1 and high-mobility group box-1 (HMGB1). Using multivariate analysis, we assessed 147 NSCLC patients and 35 control patients and found that HMGB1 and PAI-1 levels were significantly correlated with those of PDMP. We also analyzed the contribution of the newly designed risk factor (NDRF) to overall survival (OS) or disease-free survival (DFS). NDRF classification was determined based on levels of PDMP, HMGB1 and PAI-1. To determine the individual prognostic power of PDMP, HMGB1 and PAI-1, we evaluated associations between their levels and patients outcome by Kaplan–Meier survival analysis in the derivation cohort. NDRF3 status (patients who had high levels of all of PDMP, HMGB1 and PAI-1) was significantly correlated with a poor prognosis (p < 0.05 for both OS and DFS). Our findings suggest that abnormal levels of PDMP, HMGB1 and PAI-1 are related to each other in NSCLC. Moreover, the vascular complications associated with these three markers may contribute to a poor prognosis for NSCLC patients.