Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR associated protein (Cas) technology is an effective tool for site-specific genome editing, used to precisely induce mutagenesis in different plant species including rice. Salinity is one of the most stressful environmental constraints affecting agricultural productivity worldwide. As plant adaptation to salinity stress is under polygenic control therefore, 51 rice genes have been identified that play crucial role in response to salinity. This review offers an exclusive overview of genes identified in rice genome for salinity stress tolerance. This will provide an idea to produce rice varieties with enhanced salt tolerance using the potentially efficient CRISPR-Cas technology. Several undesirable off-target effects of CRISPR-Cas technology and their possible solutions have also been highlighted.