Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes that catalyze protein synthesis by charging amnio acids onto their cognate tRNAs. essential for protein synthesis, catalyzing the charging of amino acids onto their cognate tRNAs. Beyond this canonical role, mammalian ARSs exhibit diverse non-canonical functions that contribute to the maintenance of cellular and systemic homeostasis. Notably, several ARSs are secreted by specific signals and function as cytokine-like regulators with distinct biological activities. Based on these activities and their measurable level, ARS-derived biomarkers have been developed for disease diagnostics. By leveraging cancer microenvironment-associated secreted ARSs and cytokines, novel biomarkers have been identified and validated for cancer diagnosis.