In this review, we summarize CRISPR-Cas9 system-based gene modification for the therapeutic treatment of cancer. Cancer is a group of diseases involving anomalous cell growth with the potential to invade or blow out to other parts of the body, which is considered by not only multiple genetic but also epigenetic amendments that drive malignant cell propagation and consult chemo-resistance. The ability to correct or ablating such mutations holds enormous promise for battling cancer. Recently, because of its great efficiency and truthfulness, the CRISPR-Cas9 advanced genome editing technique has been extensively used in therapeutic investigations of cancers. Several studies used CRISPR-Cas9 technique for directly pointing cancer cell genomic DNA in cellular and animal cancer models, which have shown therapeutic potential in intensifying anti-cancer protocols. Moreover, CRISPR-Cas9 can also be engaged to fight oncogenic infections, discover anticancer drugs, and engineer immune cells and oncolytic viruses for immunotherapeutic treatment of cancer. We have been discussed the challenges and enhancements in translating therapeutic methods with CRISPR-Cas9 for clinical use. Therefore, in the study we suggested the potential directions of the CRISPR-Cas9 system for future cancer therapy.