Disclosed is a method for in situ detection of one or more target nucleic acids based on a combination of RNAscope® method and a general ISH signal amplification method. This new method produces high signal intensity and while keeps low background noise of signal amplification. The result can be consistently reproduced and the method can be easily adopted for routine clinic diagnostic use. Further, the invention relates to a kit, comprising the components of RNAscope® assay and a general ISH signal amplification assay, for sensitive detection of one or more target nucleic acids.