The RASSF1A (53/124, 42.74%), APC (49/123, 39.52%), ESR1 (37/124, 29.84%), ABCB1 (31/124, 24.19%, MT1G (25/124, 20.16%) and HOXC9 (17/124, 13.71%) genes were more frequently methylated in the lung tissue from the stage I NSCLC than the non-cancerous lesion patients (2/26, 7.69%, P < 0.01; 2/26, 7.69%, P < 0.01; 2/26, 7.69%, P < 0.05; 1/26, 3.85% P < 0.01; 0/26 0%, P value: <0.01; 0/26, 0%, P < 0.05, respectively). p16INK4A was methylated in 28/124 (22.56%) of cancer tissues and 2/26 (7.69%) of non-cancerous tissues (P value >0.05).