Background Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Platelet activation may play an important role in pathologic progress in lung cancer. In this study, we aimed to clarify the influence of activated platelets on lung cancer generation and growth, and the relationship among these functional and ultrastructural changes of platelets and the severity of pathogenetic condition in these patients with NSCLC.Methods One hundred and thirty-six cases of patients with pathologically confirmed NSCLC were included in this study. Fifty-four healthy people were enrolled as controls. The change of ultra microstructure and activity of blood platelets were observed under the transmission and scanning electron microscope. Simultaneous determination of plasma granule membrane protein 140 (GMP-140) was made.Results Transmission electron microscopy showed remarkable changes of ultra microstructure of platelets in patients with NSCLC, including swelling, increase of o-granules, vesicles, and glycogenosome. Scanning electron microscopy showed many more surface processes and wrinkles on platelets in patients with NSCLC. The reference plasma levels of GMP-140 of healthy controls were (18.2±2.7) μg/L. The plasma levels of GMP-140 in patients with NSCLC were (47.8±12.3) μg/L, which were much higher than those of the controls. There was a medium positive correlation between plasma levels of GMP-140 and amount of o-granules (r=0.514, P<0.01) and a high positive correlation between plasma levels of GMP-140 and area of platelet (r=0.84, P<0.01) in patients with NSCLC. The Kaplan-Meier survival curve analysis showed significant shift to the left in patients with NSCLC whose α-granules per platelet were 19 or more compared to those 18 or less (Log rank statistic, X2=17.38, P <0.01).Conclusions There are significant activated changes of ultra microstructure and increased activity of blood platelets in patients with NSCLC. These activated platelets may play an important role in the generation and growth of lung cancer. These changes can be used as a diagnostic index of severity, progression, and prognosis of NSCLC.