Since the discovery of the CRISPR-Cas9 system numerous new Cas variants have been identified with the ambition to create superior treatment approaches for various diseases including cancer. Our metagenomics screening revealed a novel Cas nuclease, termed G-daseE, which induces both collateral DNA and RNA degradation upon guide RNA-mediated recognition of a target RNA. Here we show that this RNA-inducible nuclease activity can be applied for selective elimination of cancer cells. G-daseE was assembled with target-specific gRNAs as RNP complexes and cell depletion was determined by quantitative fluorescence imaging and cytotoxicity assays. By directing RNPs against the mRNA of the housekeeping gene GAPDH, cell death could be triggered in all cell types tested including head neck and cervix cancer cell lines. Interestingly, cell elimination was also observed when the cancer-associated nuclear long non-coding RNA MALAT1 was targeted, proving the broad target RNA spectrum of G-daseE in human cells. To address selectivity, we performed co-culture experiments and achieved selective depletion of GFP-positive cells from a mixed population consisting of GFP- and RFP-expressing HEK293 cells. Finally, we targeted the clinically relevant HPV18-E6/E7 oncogenes expressed in HeLa cervix carcinoma cells and succeeded in elimination of HeLa cells whereas HEK293 cells that do not carry the oncogenic mRNA remained viable. Remarkably, creating single mismatch mutations in the targeting gRNA abolished cell killing confirming high specificity of G-daseE. Altogether, we showed that G-daseE can be programmed to induce selective cell elimination upon recognition of user-defined marker RNAs providing an innovative strategy for targeted cancer therapies.