Abstract: Objective To study the application of joint detection of feces sFRP2, Vimentin and HPP1 gene methylation in screening for early colorectal cancer. Methods Sixty patients with colorectal cancer admitted to the Third People's Hospital of Hangzhou were recruited in the colorectal cancer group. A non-colorectal cancer group(90 cases) was composed of 60 patients with adenomatous polyps and 30 normal healthy people. The stool samples were collected in early morning to extract stool DNA, And DNA was then modified with bisulfite, methylation-specific PCR was performed to detect the methylation status of sFRP2, Vimentin and HPP1 genes, and their relationship with the clinicopathological features of colorectal cancer was analyzed, and the diagnostic sensitivity and specificity of the three genes combined detection was compared. Results Among colorectal cancer patients, in the test of single gene methylation the sensitivity for sFRP2, Vimentin and HPP1 were 46.7%, 43.3%, 53.3%,respectively; and the specificity for sFRP2, Vimentin and HPP1 was 73.3%, 75.6%, 76.7% respectively; the combined test group had 3 genes One of the genes was positive for methylation expression. The sensitivity was 83.3% and the specificity was 46.7% which was higher than that of sFRP2, Vimentin and single gene test alone. The methylation status of the three genes was not related to the gender, age, tumor site, lymph node metastasis and TNM stage of colorectal cancer patients(all P>0.05). Conclusion The incidence of abnormal methylation of sFRP2, Vimentin and HPP1 genes in fecal DNA of colorectal cancer patients is significantly higher than that of non-colorectal cancer patients. The combined test of stool DNA in screening for colorectal cancer is superior to single gene test in early stage of colorectal cancer It is of great significance in screening applications.