In the present study, we sought to investigate the potential interrelationship of expression of RUNX3, H3K27me3 and its methyltransferase EZH2 in NSCLC patients, their correlation with clinicopathologic parameters, and the prognostic significance as well, finding that expression of RUNX3 was closely correlated with H3K27me3 and their co-expression was significantly associated with better prognosis especially in either stage I or postoperative chemotherapy-naive (POCT-naive) NSCLC patients. The gene discussed is EZH2; the disease is non-small cell lung carcinoma.