Lung cancer is one of the deadliest cancers. In the US, about 226,650 new lung cancer cases are expected for 2025. Most lung cancers (~87%) are the common type called non–small cell lung cancer (NSCLC). Current diagnostic approaches—including low-dose CT imaging and tissue biopsy—are limited by high false-positive tests, radiation exposure, and invasiveness. Early detection can reduce treatment-related harm and death. We evaluated a non-invasive liquid-biopsy strategy based on circulating transfer RNAs (tRNAs) for the early diagnosis of NSCLC. Using several datasets from independent population groups, we identified a 6-tRNA panel that accurately distinguishes cases from controls, with strong performance in early-stage disease. Preliminary functional analyses of the tRNAs suggest that several of these tRNAs may promote tumor growth. These findings support using circulating tRNAs as biomarkers for NSCLC screening and early detection, in hopes of saving lives.