When analyzing tumor tissues, we observed that the advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status, with adjusted HRs (95% CI) of 9.64 (2.92–31.81), 8.29 (3.40–20.22), and 11.83 (3.49–40.12), respectively. Here, MGMT is linked to neoplasm.