There are great demands of robust diagnostic and prognostic approaches for HCC. DNA methylation, an epigenetic modification, has been found enrich in gene promoters leading to the occurrence of cancer. The adsorption affinities between different DNA bases and AuNPs are not the same, which can be applied to distinguish adenine-enriched sequence from guanine-enriched sequence. Herein a simple and low-cost reginal DNA methylation detection method was demonstrated. A home-made AuNPs-SPCE was employed to achieve the DNA methylation detection, and several factors including adsorption time, adsorption temperature and sample concentration were investigated and optimized.