Platelet-derived microvesicles (PMVs) and their encapsulated microRNAs (miRNAs) hold immense potential as biomarkers for early non-small cell lung cancer (NSCLC) diagnosis. This study presents a pioneering liposome-based approach for enhanced miRNA detection within PMVs, employing a lambda exonuclease (λ EXO)-based amplification system encapsulated in immunoliposomes. The platform exploits the novel catalytic functionality of λ EXO, demonstrating its unprecedented capability to catalyze RNA-DNA hybrid substrates. The λ EXO-based amplification system exhibited high sensitivity and specificity in detecting miRNA-21, a key miRNA associated with NSCLC, demonstrating a limit of detection (LOD) of 33.11 fg mL