The article introduces a genetically encoded CRISPR-based imaging system called fluorogenic CRISPR (fCRISPR) for high-contrast and sensitive imaging of genomic DNA in living cells. fCRISPR combines dCas9, an engineered sgRNA, and a fluorogenic protein. The fluorogenic protein is degraded unless bound to specific RNA hairpins, which are inserted into the sgRNA. This results in a ternary complex that enables specific and efficient imaging of genomic loci. The system overcomes the limitations of conventional CRISPR-based tools, which often involve constitutively fluorescent proteins that lead to high background fluorescence and nonspecific signals. fCRISPR demonstrates high signal-to-noise ratio and sensitivity, allowing for the imaging of various genomic loci in different human cell lines. It also enables the tracking of chromosome dynamics, telomere length, and DNA double-strand breaks and repairs in real-time. The low background fluorescence and high sensitivity of fCRISPR make it a robust platform for genomic DNA imaging.The article introduces a genetically encoded CRISPR-based imaging system called fluorogenic CRISPR (fCRISPR) for high-contrast and sensitive imaging of genomic DNA in living cells. fCRISPR combines dCas9, an engineered sgRNA, and a fluorogenic protein. The fluorogenic protein is degraded unless bound to specific RNA hairpins, which are inserted into the sgRNA. This results in a ternary complex that enables specific and efficient imaging of genomic loci. The system overcomes the limitations of conventional CRISPR-based tools, which often involve constitutively fluorescent proteins that lead to high background fluorescence and nonspecific signals. fCRISPR demonstrates high signal-to-noise ratio and sensitivity, allowing for the imaging of various genomic loci in different human cell lines. It also enables the tracking of chromosome dynamics, telomere length, and DNA double-strand breaks and repairs in real-time. The low background fluorescence and high sensitivity of fCRISPR make it a robust platform for genomic DNA imaging.