CRISPR based high-throughput screening is a large-scale genetic loss-of-function experimental approach that facilitates discovery of key genes or gene sequences that correlate with a specific function or phenotype for a cell type, for example, resistance or sensitivity to a drug, susceptibility to environmental toxins, components of a cellular pathway or novel pathogenic biomarkers. Recently, using CRISPR screens a compelling lethal interaction between the helicaseencoding WRN gene and microsatellite instability was identified. In immuno-oncology, the molecular mechanism of tumor immune evasion was explored which included multiple factors like Ras signaling, antigen presentation, interferon, autophagy, and epigenetic remodeling. In another study, a CRISPR based screening approach showed that depletion of neurofibromin, merlin and the mediator complex component MED12 conferred resistance to vemurafenib, a B-Raf enzyme inhibitor, in BRAF-mutant melanoma cells. In the future, CRISPR/Cas9 based efficient and precise cancer models and highthroughput screens are likely to significantly promote functional cancer genomics research and accelerate the development of novel cancer therapies.