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Tumour M2‐pyruvate kinase (TUM2‐PK) is up‐regulated in many human cancers. This study was to evaluate the clinical value of serum TUM2‐PK in early‐stage non–small cell lung cancer (NSCLC) patients. A total of 162 consecutive early‐stage NSCLC patients were enrolled and followed up after tumour resection. Serum TUM2‐PK level was detected by enzyme‐linked immunosorbent assay (ELISA) in NSCLC patients, 50 benign pulmonary disease patients and 102 healthy controls. The TUM2‐PK level in NSCLC patients was higher than that of healthy controls (P <.001) and benign pulmonary disease patients (P <.001). A threshold of 30 U/mL could be used to diagnose early‐stage NSCLC with 71.6% sensitivity and 98.0% specificity. The 5‐year overall survival rate in patients with high TUM2‐PK level was lower than that of patients with low TUM2‐PK level (P =.009). Multivariable Cox regression showed that high TUM2‐PK level was an independent risk factor for overall survival (HR = 2.595, 95% CI: 1.231‐5.474, P =.012). High serum TUM2‐PK level could be a potential biomarker for diagnosis and prognosis of early‐stage NSCLC patients. [ABSTRACT FROM AUTHOR]