In this study, we revealed for the first time ZNF191 can bind to the DNMT1 promoter directly, transactivate the DNMT1 gene, induce DNMT1 mRNA and protein expression, and cause DNA methylation alteration in hepatoma cells, which may promote hepatoma cell proliferation by activating the PI3K‐AKT pathway. This evidence concerns the gene AKT1 and hepatocellular carcinoma.