The regulatory mechanism involves in the increased expression of p53 and following DNMT1, which further induce hypermethylation in the promoter region of CLIC4. Exploration of the methylation status of CLIC4 promoter and its transcribed mRNA level in malignant lung cancer and normal fibroblast cells revealed the highly methylated status in the malignant cells expressing lower mRNA levels of CLIC4. In the future, it is worthwhile to further address whether modulating the DNMT1 activity to regulate the CLIC4 expression could become a novel approach to inhibit the tumor malignancy. This evidence concerns the gene TP53 and lung carcinoma.