We constructed a novel surface plasmon resonance (SPR) detection assay using carboxyl-functionalized molybdenum disulfide (carboxyl-MoS2) nanocomposites as a signal amplification sensing film for the ultrasensitive detection of the lung cancer-associated biomarker cytokeratin 19 fragment (CYFRA21-1). This evidence concerns the gene KRT19 and lung carcinoma.