Objective To assess the performance of the methylation‐sensitive high‐resolution melting curve analysis (MS‐HRM analysis) on the detection of the methylation in stool DNA for colorectal cancer screening .Methods Eighty‐two qualified stool samples were collected from 27 patients with colorectal cancer patients (CRC group) ,25 patients with advanced adenomas (AA group) ,and 30 healthy people (control group) .The methylation status of vimentin gene in all of the stool samples was detected by the MS‐HRM analysis on the LightCycler 480 platform .The fecal occult blood test (FOBT) was also used for the same samples . Results The positive rates of the MS‐HRM assay in the CRC group ,AA group ,and control group were 81 .5% (22/27) ,80 .0%(20/25) ,and 6 .7% (2/30) respectively .The positive rates of FOBT in the three groups were 37 .0% (10/27) ,12 .0% (3/25) and 3 .3% (1/30) respectively .The diagnostic sensitivity of the MS‐HRM assay for colorectal cancer and advanced adenomas (80 .8% , 42/52) was significantly higher than that of FOBT (25 .0% ,13/52)(P<0 .05) .No significant difference was found in the diagnos‐tic specificity between the MS‐HRM assay (93 .3% ,28/30) and the FOBT (96 .7% ,29/30) (P>0 .05) .Conclusion MS‐HRM performs better than FOBT and has great application potential in the detection of stool DNA methylation for colorectal cancer screening .