Aims: This study aims to explore a reliable screening method for early detection of endometrial carcinoma (EC) using a methylation marker in endometrial brush (Tao brush) samples since there is currently no effective, minimally invasive screening method for EC. Methods: The methylation data of EC and normal endometrial tissues from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were used for analyses. Next, we concentrated on HIST1H4F and detected the methylation in 121 endometrial tissues and 118 Tao brush samples by optimized methylation-sensitive restriction enzymes combined with quantitative real-time PCR (McRe-qPCR), and evaluated it as a biomarker for early EC screening. Results: Compared with normal tissues, the significant hypermethylation of HIST1H4F in EC was verified in endometrial tissues from TCGA and GEO datasets with areas under the curve (AUC) > 0.975, which was verified in clinical samples. In Tao brush samples, the sensitivity and specificity of HIST1H4F hypermethylation in detecting EC were 88.64% and 84.00%. It indicated good classification accuracy in the detection of Stage I EC with a sensitivity of 88.64% and a specificity of 85.37%. Conclusion: Hypermethylated HIST1H4F could provide a minimally invasive approach for early detection of EC to complement existing hysteroscopy.