Surgical resection, providing a long-term survival of hepatocellular carcinoma (HCC) patients, is regarded as one of the standard curative treatments of HCC if the tumor is resectable. However, 50% patients develop early recurrence (ER) during the first two years after operation, which are more diffuse and rarely treatable with unsatisfactory long-term survival. Unfortunately, the underlying mechanisms of ER after curative resection and the molecular markers with predictive and prognostic significance have never been identified yet. Recent studies reveal that pyruvate kinase M2 (PKM2) levels were correlated with overall survival and disease-free survival in patients with HCC. The present study was aimed to investigate the correlation between the expression of PKM2 and ER. Our findings demonstrated that not the total PKM2 expression but the nuclear PKM2 expression as an independent risk factor for ER after curative resection, and could be a promising intervention target following curative resection for HCC patients.