At present, 2019 novel coronavirus (2019-nCoV) mutations occur frequently, and the current mutation, represented by omicron, has significantly enhanced its transmission and greatly increased the difficulty of prevention and control of Coronavirus Disease 2019 (COVID-19). In order to effectively deal with the epidemic situation of COVID-19, it is urgent to develop accurate, sensitive and field-applicable diversified detection techniques for the mutants. In this review, we introduce the current technical method for 2019-nCoV detection, focus on the application of different method in mutation detection, and analyze their advantages and disadvantages. In addition to the traditional detection techniques such as nucleic acid and immunity, we also discuss the importance of establishing phenotypic correlation detection method such as affinity of 2019-nCoV mutants. It is meaningful for accurately detecting and analyzing the important indexes such as infectivity and pathogenicity of the mutant, as well as for improving the efficiency of epidemic screening and its treatment.