Early diagnosis of cancer can significantly decrease the mortality rate, and improve the effectiveness of treatment. However, early diagnosis leads to an increased and additional burden of medical resources. Lung cancer with the highest incidence and mortality rate of cancer presents a great challenge to the health of human beings. Non-small cell lung cancer (NSCLC), accounting for approximately 85 % of all lung cancer, desires a diagnostics method with low-cost, high accuracy, easy-operation, and fast speed. Recent research highlights the diagnostic potential of exosomes, particularly programmed death-ligand 1 (PD-L1) exosomes, which play a critical role in NSCLC by facilitating tumor cell immune evasion. This study introduces an organic electrochemical transistor (OECT)-based biosensor equipped with a carbon nanofibers-gold nanoparticles (CNFs-GNPs) gate electrode with super high surface area for detecting PD-L1 exosomes from micro-liters blood samples. The optimal stability, biocompatibility, and detection accuracy are systematically studied. The OECTs realize high sensitivity and selectivity, characterized by a transconductance of 66.7 mS, a rapid response time of about 42 ms, and less than 6 % current change after 2000 s of cycling. By immobilizing the PD-L1 aptamer on CNFs-GNPs via gold-sulfur bonding, the biosensor detects PD-L1 exosomes with a sensitivity as low as 10 pg/mL. Clinical trials using micro-liters blood has shown distinct differences between NSCLC patients and healthy individuals, suggesting this technology could significantly enhance early NSCLC detection and expand to other cancer diagnostics.