The invention relates to a method for simultaneously detecting microsatellite locus stability and genome change on the basis of second generation sequencing, especially an application of the detection method in assisting in diagnosing a colorectal cancer patient and a corresponding kit. According to the method provided by the invention, the sequence analysis for a plurality of samples can be completed at one time; the detection for genome change, such as, gene mutation and chromosome variation, is completed while the detection for the microsatellite state is completed; no additional experimental operation is required; the analysis time and the cost for detecting the patient are greatly saved; compared with PCR electrophoretic MSI detection gold standard, the detection method provided by the invention has the advantages of matching accuracy, high detection speed, lower price and no dependence on a matched normal sample, so that the detection mode is more convenient.